The Red Devils sit three points behind the perfect Real Sociedad in second place, while the Moldovan visitors to Old Trafford are third in the group having claimed just one win so far.
Match preview
Having acted as Man United's midfield general during their clash with Chelsea at Stamford Bridge, Casemiro made a crucial contribution at the other end of the field to rescue a last-gasp point for the Red Devils after Jorginho had opened the scoring from the spot.
Scott McTominay mindlessly brought Armando Broja down in the box to present Jorginho with the chance to break the deadlock, but Casemiro's header met both the fingers of Kepa Arrizabalaga and the inside of the post before trickling over the line and sparking jubilant scenes from the away end.
Erik ten Hag's men are still playing catchup in the race for a top-four place, and it is a similar story in the Europa League, with Real Sociedad still sitting pretty at the top of Group E with 12 points as Man United occupy the runners-up spot at present.
A magnificent showing from stand-in Omonia goalkeeper Francis Uzoho ultimately went unrewarded on matchday four, as McTominay crashed home the late winner to leave Man United needing just a point from their final two games to advance to the knockout rounds.
The Red Devils enter Thursday's game having gone unbeaten in their last six games in all tournaments, and despite going down to Real Sociedad at Old Trafford on September 8, not since the 1996-97 Champions League have Man United lost two group-stage European games in a single campaign at the Theatre of Dreams.
A recent switch to a three-man backline has not had the desired effect for Sheriff Tiraspol, who began life in the Europa League with an eye-catching 3-0 win over Omonia, but the Moldovan powerhouses have since struggled to mix with the Group E big boys.
After being put to the sword 2-0 by Man United on matchday two, Sheriff has since suffered a pair of similarly comprehensive defeats to Real Sociedad by an aggregate score of 5-0, and any slim hopes the visitors have of making the knockout rounds will be dashed if they fail to win at Old Trafford.
Battling pointless Omonia for the consolation prize of Europa Conference League football is now the most likely outcome for Stjepan Tomas's men, who suffered a rare top-flight defeat at the weekend, going down 1-0 to Petrocub courtesy of Vladimir Ambros's header on the stroke of half time.
A period of inconsistency from the Moldovan champions has seen them win just four of their last nine matches in all competitions, and they have only ever won three Europa League games away from home in their history, so their chances of becoming the first-ever Moldovan side to beat English opposition in Europe are not exactly high.
Jadon Sancho and the recently-axed Cristiano Ronaldo were on target as Man United overcame Sheriff 2-0 earlier this season, and Ten Hag will be desperate to see his crop put in a free-flowing to divert attention away from the seemingly never-ending Ronaldo saga.
Manchester United Europa League form:
L
W
W
W
Manchester United form (all competitions):
W
W
W
D
W
D
Sheriff Tiraspol Europa League form:
D
W
W
L
L
L
Sheriff Tiraspol form (all competitions):
Team News
In a major blow for both club and country, Raphael Varane was forced off the Stamford Bridge turf in tears at the weekend with a knee injury, and he is not expected to play for Man United again before the World Cup. As a result, Victor Lindelof will deputise this week.
Much of the pre-match talk at Stamford Bridge centred around the absence of Cristiano Ronaldo, who was dropped from the squad after refusing to come on as a substitute in the win over Tottenham Hotspur, and it remains to be seen if he will be considered for a recall against one of just two sides he has netted against this term.
Harry Maguire, Aaron Wan-Bissaka and Anthony Martial are all back in training for the Red Devils, but Brandon Williams, Axel Tuanzebe and Donny van de Beek remain in the infirmary. Either way, Ten Hag should stick with a first-choice XI in a bid to wrap up qualification as soon as possible.
Meanwhile, Sheriff's recent issues have been disciplinary-related rather than injury-borne, as right-back Armel Zohouri will sit this one out after being sent off in the 3-0 loss to Sociedad on matchday four.
In brighter news, Iyayi Atiemwen and Moussa Kyabou are both eligible to return after serving suspensions of their own last time out, but the latter has missed his side's last three domestic matches for unknown reasons.
Maksym Koval has recently lost his place in goal to Dumitru Celeadnic, who should start at Old Trafford, while Atiemwen could join Rasheed Akanbi and Felipe Vizeu in the final third upon his return.
Manchester United possible starting lineup:
De Gea; Dalot, Lindelof, Martinez, Shaw; Casemiro, Eriksen; Antony, Fernandes, Sancho; Rashford
Sheriff Tiraspol possible starting lineup:
Celeadnic; Kiki, Radeljic, Kpozo; Guedes, Badolo, Salifu, Heron; Akanbi, Vizeu, Atiemwen
We say: Manchester United 2-0 Sheriff Tiraspol
Coming away from Stamford Bridge with just a point to their name would have disappointed a dominant Man United, who blew Tottenham away at Old Trafford last week and should have no trouble inflicting similar punishment on Sheriff.