Bayern are ten points clear at the top of the league and an away win at Mainz will guarantee the title with three games remaining.
Head coach Hansi Flick dropped a bombshell last weekend by saying he wants to be released from his contract at the end of the term and wants to sign off with the league title.
The Bavarians are boosted by the presence of Lewandowski, who has missed their last six games with a knee injury.
The Poland striker has netted 35 goals this season and is five short of Gerd Mueller’s all-time league record of 40 set in 1971/72.
“I don’t know if I’ll do it yet,” Lewandowski said on Wednesday.
“But I hope that when I’m back on the pitch, I can be at my usual level from the first minute and score goals.”
Mainz have won four of their last six games to pull clear of the relegation battle, but they last beat Bayern five years ago.
Germany winger Serge Gnabry could be included in the Bayern squad after resuming training for the first time since testing positive for Covid-19.
Elsewhere, Borussia Dortmund are running out of chances to qualify for the Champions League, but can take a step closer to the European top-tier at third-placed Wolfsburg on Saturday.
The top four of the Bundesliga qualify for the Champions League with Dortmund currently fifth, five points behind Wolfsburg.
Dortmund defender Mats Hummels is suspended after picking up a fifth yellow card this season in Wednesday’s 2-0 home win over Union Berlin.
Dortmund’s hopes could also be boosted if fourth-placed Eintracht Frankfurt, who are one place and four points ahead of them, struggle again at Bayer Leverkusen.
Frankfurt have lost their last six league games at Leverkusen, but claimed a 2-0 win at home to Augsburg on Tuesday with top-scorer Andre Silva heading in his 24th league goal this season.
With four games left, Frankfurt are on course to qualify for the Champions League for the first time.
“Now is the phase when you have to collect points,” said Frankfurt coach Adi Huetter, who is leaving to take charge of Borussia Moenchengladbach next season.
“Dortmund are under much more pressure than us.”
There is a question over Frankfurt’s Japan midfielder Daichi Kamada, who suffered a freak finger injury at home.
The 24-year-old played on Tuesday with the finger heavily strapped, but Huetter said the digit “throbbed” causing discomfort.
The England winger returned from injury on Tuesday to make his 100th Bundesliga appearance and could be a key factor in Dortmund’s crunch tie at Wolfsburg on Saturday.
Fitness issues and a dip in form have meant the 21-year-old has struggled to match last season’s tallies of 17 goals and as many assists.
Dortmund’s hopes of a win at Wolfsburg will be boosted if Sancho quickly rekindles his partnership up front with Erling Braut Haaland.
Six – of Sancho’s 11 Bundesliga assists this season have led to goals by Haaland.
50 – assists for Sancho in 100 Bundesliga appearances since he joined from Manchester City in 2017.
42 – goals Lewandowski has scored this season in 36 games for Bayern in all competitions.
Fixtures (all times 1330GMT unless stated)
Augsburg v Cologne (1830)
VfL Wolfsburg V Borussia Dortmund, Freiburg v Hoffenheim, Union Berlin v Werder Bremen, Mainz v Bayern Munich, Bayer Leverkusen v Eintracht Frankfurt (1630)
RB Leipzig v VfB Stuttgart, Borussia Moenchengladbach v Arminia Bielefeld (1600)
Postponed – Schalke 04 v Hertha Berlin