Philadelphia vs. Atlanta (Saturday, 8.30pm)
Playoff hopefuls Philadelphia Union and Atlanta United will lock horns in their Eastern Conference match when the pair meet at Subaru Park on Saturday evening.
Just one place and one point separate the two in the table, with both sides desperate for a win to strengthen their position in the top seven.
We say: Philadelphia Union 1-1 Atlanta United
Not much separates these two sides in the table and there is nothing really to suggest much separates the pair on the pitch.
Atlanta do boast a superior head-to-head record against the Union, yet United have not been up to their usual lofty standards in the past couple of seasons, making the draw a likely outcome for this one.
New England vs. Orlando City (Sunday, 12.00am)
With a playoff berth officially sewn up this week, the New England Revolution will hope to increase their lead atop the Eastern Conference standings when they host Orlando City on Saturday from Gillette Stadium.
The Revs are on a seven-game winning streak at home with a 13-point lead in the race for the Supporters' Shield, while the Lions are looking to snap a seven-match losing run on the road.
We say: New England Revolution 3-1 Orlando City
The Revs know how to find the back of the net, and they do it a lot at home with 12 in their last five games, and even though their lead is quite comfortable at the moment, they still want to make more history.
Orlando look like they have unravelled with three red cards in their last two games, and they are winless in their previous seven road fixtures, with a number of lopsided defeats.
Columbus Crew vs. Montreal (Sunday, 12.30am)
Reigning Major League Soccer Cup champions Columbus Crew will continue their pursuit of a place in the 2021 playoffs when they welcome CF Montreal to Lower.com Field on Sunday.
Four points off seventh place and with only one win in four, the Crew will be desperate for an upturn in form when they face their Canadian opponents.
We say: Columbus Crew 1-2 CF Montreal
Two-times winners of the MLS Cup, the Crew may have been hoping for a better defence of their title and still could make a late dash for the playoffs.
However they have not looked like the same side that triumphed just less than a year ago and the form table suggests that Montreal could leave the States with a precious victory.
DC United vs. Cincinnati (Sunday, 12.30am)
DC United will look to mount the pressure on their fellow playoff hopefuls when they welcome strugglers FC Cincinnati to Audi Field on Sunday morning.
Only once in four meetings has this fixture not finished goalless, with both sides desperate to avoid another stalemate and take all three points.
We say: DC United 3-0 FC Cincinnati
Both sides are in need of the points for two completely different reasons; DC United are keen to book themselves into this year's playoffs, whilst Cincinnati will be looking to avoid finishing bottom of the Eastern Conference.
The head-to-heads suggest a stalemate, whilst the form book points towards a DC United win - it may not be entirely one-sided, but the Black-and-Red should have enough.
NY City vs. NY Red Bulls (Sunday, 12.30am)
For the second time in three days, New York City FC will take on their biggest rivals, the New York Red Bulls, in the Hudson River Derby on Saturday from Yankee Stadium.
On Wednesday, the Red Bulls salvaged a point with an equaliser in injury-time while the Boys in Blue extended their unbeaten run to three with that 1-1 draw.
We say: New York City FC 2-0 New York Red Bulls
The Pigeons have gone up against some of the top attacking sides in MLS at home this year and have done a great job of shutting them down, plus their top goalscorer has really been in the mood to score of late, and he loves playing the Red Bulls, having notched four goals against them in his career.
Minnesota Utd vs. Houston (Sunday, 1.00am)
Minnesota United are currently one point ahead of Los Angeles FC, who sit in eighth, with a game in hand on their nearest playoff rivals, potentially giving Adrian Heath's side the opportunity to climb up to fourth starting with a win against Sunday's opponents Houston Dynamo.
The visitors have recently broken a poor run of form by going three games unbeaten heading into this Western Conference fixture, but they have most probably left themselves with too much to do to reach the top seven.
We say: Minnesota United 2-1 Houston Dynamo
Minnesota will take confidence from their result against LA Galaxy, and will be aiming to follow that up with another victory at home, and Dynamo's unbeaten run could be ended, taking into consideration their poor away record.
The front four were all involved in all three of Minnesota's goals against Dallas, and they will fancy their chances against a Houston defence which has conceded 39 goals in 26 matches this season.
Colorado vs. Toronto (Sunday, 1.00am)
Toronto will travel South across the border and through the Rocky Mountains to face Colorado Rapids in one of the pair's cross-conference games on Sunday morning.
The Rapids are chasing a maiden Supporters' Shield, whilst Toronto are on course for their worst-ever finish in Major League Soccer.
We say: Colorado Rapids 2-1 Toronto
Two sides who could not be in more contrasting form, all signs point to a comprehensive victory for the Rapids, who will be aware of the fact they could top the Western Conference with a win.
Toronto will be hoping the unpredictability of the cross-conference matches could help their cause and, buoyed by two consecutive wins, they may be able to push the Rapids closer than expected.
Vancouver vs. Dallas (Sunday, 3.00am)
Dallas are hoping that a new face on the sidelines can turn around their fortunes in the Western Conference as they travel to beautiful British Columbia to face the Vancouver Whitecaps on Saturday at BC Place Stadium.
The Caps earned a big 1-1 draw on the road against the Colorado Rapids last weekend, while the Toros are now seven points back of a playoff position after dropping a 3-2 decision to the Houston Dynamo.
We say: Vancouver Whitecaps 3-1 Dallas
Usually, a coaching change can produce early success for a team, but in the Toros' case, leadership was not the only issue as they have been susceptible to conceding on the road all year long, and the Caps have been splendid in transition on their home field.
Earthquakes vs. Los Angeles (Sunday, 3.00am)
One of the oldest rivalries in American soccer will take place on Saturday at PayPal Park as the San Jose Earthquakes host Los Angeles FC.
The Quakes won the first game in the California Clasico this season, 2-1 back in August, but LA are ahead of them in the Western Conference standings by three points heading into this match.
We say: San Jose Earthquakes 2-1 Los Angeles FC
Even though the Quakes have been poor defensively of late, they can probably afford to play more wide open against their state rivals, who seem to squander a lot of great scoring opportunities and are still without some of their top attacking options.
Portland vs. Salt Lake (Sunday, 3.30am)
Two sides separated by just one point in the MLS Western Conference standings will hope to maintain their playoff positions as the Portland Timbers host Real Salt Lake on Saturday from Providence Park.
Portland have come to life, currently in fifth, unbeaten in their last five games, while Claret and Cobalt have squeaked out a pair of one-goal victories as they sit in sixth, but only three points clear of eighth-place Los Angeles FC.
We say: Portland Timbers 2-2 Real Salt Lake
When these two teams meet in Portland, it is traditionally a joy to watch for neutral fans as there have been 13 goals scored between them in the last two matches played at Providence Park.
There is a lot more consistency to the Timbers game of late, but Salt Lake are at their best when their backs are up against the wall, and that might be the case for them this weekend as a loss could drop them below the playoff line.