The visitors, meanwhile, have already secured their progression to the knockout stages, and they could have top spot in Group E confirmed in midweek.
Match preview
Santos, on the other hand, trail Chilean side Audax Italiano by three points with two matches of the group stage remaining, meaning they must win at least one of their final two games if they are to have any chance of progressing in South American's secondary continental competition.
The two teams have already played each other twice, so Odair Hellmann's side will not have the opportunity to directly close the gap to the second-placed side in the group. As such, they are relying on favours elsewhere.
However, all Peixe can do is focus on their own results, which have taken a downward turn in recent weeks. Indeed, Hellman's side have failed to win any of their last five matches in all competitions, which has seen them crash out of the Copa do Brasil and drop to 12th in Campeonato Brasileiro Serie A.
There is still an awfully long way of the domestic season to go, of course, but they are likely to have one eye on Audax Italiano's result against Blooming in midweek, which they simply must at least match in order to remain in the Copa Sudamericana.
Newell's OB, meanwhile, can relax in the comfort that they have already secured safe passage to the last 16 after winning all four of their group games so far.
La Lepra - who are perhaps most famous for being Lionel Messi's lifelong team after the the Argentina legend came through their youth academy - are clearly making a real fist of the Copa Sudamericana this season having never before lifted a continental competition.
Managed by former Manchester United defender Gabriel Heinze, Newell's OB remain on course to qualify for the upper half of the second stage of Argentina's Primera Division, with four points from their last two matches seeing them move into 10th in the table.
However, Heinze will be keen for his players to maintain their 100% record in the Copa Sudamericana when they travel to Brazil in midweek, especially as they would wrap up top spot with a game to spare should they manage to do so.
Santos Copa Sudamericana form:
W
D
L
L
Santos form (all competitions):
W
D
L
L
L
D
Newell's Old Boys Copa Sudamericana form:
W
W
W
W
Newell's Old Boys form (all competitions):
D
W
L
W
W
D
Team News
Santos will remain without Lucas Braga and Felipe Jonatan due to long-term groin and knee injuries respectively, while Joaquim Henrique is suspended after being sent off during his side's defeat to Audax Italiano last time out in this competition.
Renyer, Felipe Jonatan, Sandry, Luan Dias and Alex are also all major doubts for the hosts, leaving Hellmann with a major injury crisis to overcome as he attempts to keep his side in the tournament.
Newell's OB, meanwhile, will travel without Pablo Perez, Francisco Gonzalez and Fabian Angel due to knee issues.
With his side's progression to the last 16 already complete, Heinze may be weighing up making some alterations to his starting XI, but he may be tempted to go strong once again in the hope that he can rest all of his key players in the final game of the group stage.
Santos possible starting lineup:
Paulo; Lucas, Maicon, Messias, Pires; Fernandez, Alison; Ruiz, Camacho, Gabriel; Washington
Newell's Old Boys possible starting lineup:
Hoyos; Castro, Ortiz, Ditta, Pitton; Gomez, Sforza, Portillo; Tica, Recalde, Aguirre
We say: Santos 1-0 Newell's Old Boys
Santos will surely be more motivated to win this match than their opponents, who know that avoiding defeat in their final group game against Audax Italiano will be enough for them to secure first position in Group E.
As such, we expect the hosts to edge a tight encounter, which would ensure that they remain in the competition heading into the final matchday.