Leipzig, meanwhile, must win in order to keep their slim hopes of catching league leaders Bayern Munich alive.
Schalke managed to end a run of three consecutive defeats with a 1-1 draw at Werder Bremen last weekend, but Christian Gross's side need wins on the board and fast if they are going to execute one of Europe's greatest ever escapes from relegation.
The Bundesliga's worst performing side have certainly looked a slicker outfit since Gross took charge, though, with Omar Mascarell capping off a fine team move with a nicely-placed finish from the edge of the area. Unsurprisingly, Armine Harit was at the heart of almost everything positive Schalke produced on the day, with Matthew Hoppe spurning an early chance.
However, Bremen made three substitutions at half time and improved immeasurably as a result, with two of them combining for the equaliser when Milot Rashica teed up Kevin Mohwald. Maximilian Eggestein thought he had won it with only minutes remaining, only for Theodor Gebre Selassie to be correctly adjudged to have been offside in the build-up.
Gross's hopes of delivering a trophy came to an end with a 1-0 defeat to Wolfsburg in the DFB-Pokal on Wednesday, too, but the defeat does at least allow him to fully concentrate on overseeing a miraculous survival in the league.
Leipzig, meanwhile, comfortably overcame Bayer Leverkusen last weekend, with the 1-0 scoreline flattering the visitors on the day.
Florian Wirtz and Lucas Alario did come close to scoring on a couple of occasions, but Leipzig certainly should have had more goals themselves in a controlled performance. Marcel Sabitzer's early effort was correctly disallowed for an offside, with Christopher Nkunku smashing Julian Nagelsmann's ahead after half time with a superb first touch teeing up his accurate strike into the top corner.
A more likely trophy for them this season may well be the DFB-Pokal, with Wednesday's 4-0 win over VfL Bochum taking Leipzig into the quarter-final. After losing 3-0 to Bayern in the 2019 final, Nagelsmann would surely revel in delivering Leipzig's first ever major trophy to the club.
Schalke 04 Bundesliga form: LWLLLD
Schalke 04 form (all competitions): WLLLDL
RB Leipzig Bundesliga form: WLDWLW
RB Leipzig form (all competitions): LDWLWW
Nabil Bentaleb is still effectively persona non grata at the club after his disciplinary issues in November, with Shkodran Mustafi perhaps having to wait for his first start having joined from Arsenal on transfer deadline day.
Nagelsmann is likely to shuffle the pack once more, with Yussuf Poulsen pushing for a start after his brace in the cup in midweek.
Schalke 04 possible starting lineup:
Fahrmann; Becker, Thiaw, Nastasic, Kolasinac; Mascarell, Stambouli; Schopf, Uth, Harit; Hoppe
RB Leipzig possible starting lineup:
Gulasci; Mukiele, Upamecano, Halstenberg; Adams, Sabitzer, Haidara, Angelino; Olmo, Nkunku; Sorloth
We say: Schalke 04 0-2 RB Leipzig
Given that Leipzig have the tightest defence in the Bundesliga, it is difficult to envisage Schalke threatening Nagelsmann's side on too many occasions.
Leipzig should control the game almost from start to finish as they look to keep the pressure on Bayern.