Massimiliano Allegri's side will be desperate for three points to reignite its push for the top three against a Viola outfit still reeling from a 2-1 loss to Napoli.
Massimiliano Allegri's men have slipped to 10th in the Serie A table having won just two of their last nine matches in all competitions.
Milan's slow start means qualification for the Champions League appears unlikely, with the San Siro outfit needing to dramatically improve if it is to challenge for a top-three finish.
No side in the top 10 has leaked more than the 17 conceded by Milan, which has also been unable to find a regular source of goals in the absence of Stephan El Shaarawy (foot) and Giampaolo Pazzini (knee).
Lazio held Milan to a 1-1 draw on Wednesday, with French defender Mickael Ciani scoring a 72nd-minute equalizer at San Siro after Kaka had handed the home side the lead.
Despite the result, Allegri expressed satisfaction at his team's display and wants to see more of the same against Fiorentina.
"We have to keep working and putting in this sort of performance," he told Sky Sport Italia. "The side played well in terms of technique and defending, but we lost our unity a little after the equalizer and allowed a couple of dangerous counterattacks.
"After going 1-0 up we didn't take some more chances, but then with this goal we were caught out after a corner and got punished."
Milan has lost its last two home matches against Fiorentina and will once again be without Philippe Mexes, who serves the last installment of a four-match suspension.
Fellow defenders Daniele Bonera and Matias Silvestre are also absent, but goalkeeper Christian Abbiati could return from a calf injury.
Fiorentina enters the fixture in sixth place following a 2-1 home defeat to Rafael Benitez's Napoli on Wednesday.
That was the club's first defeat in seven matches, ending a run of form that included a come-from-behind 4-2 victory over reigning champion Juventus.
Fiorentina has lost just one of its seven competitive away games this term and boasts the league's top scorer in Giuseppe Rossi.
The former Villarreal striker has made a superb return from a serious knee injury and already has nine goals to his name.
Argentinian defender Gonzalo Rodriguez will return from suspension for Fiorentina, while Mario Gomez and Massimo Ambrosini are doubts after they missed the Napoli defeat.
Juan Cuadrado received two yellow cards for simulation against Napoli, although Fiorentina has appealed his resulting one-game ban.