Inter, Roma and Juventus will have to put European heartbreak swiftly behind them as they turn their attention back to domestic action this weekend.
All three Italian teams were knocked out of the UEFA Champions League by English opposition this week in the last-16.
Inter, who were beaten 2-0 by Manchester United, currently hold a seven-point advantage at the top of the table over Juve, and coach Jose Mourinho is confident his team will push on to clinch the Scudetto.
On Sunday night they face a Fiorentina side - who were the first Italian club to get knocked out in this seasons Champions League at the group stage - equally as desperate for victory.
Club owner Diego Della Valle publicly slammed the team following their 2-0 home defeat to Palermo last weekend - a match which saw them booed off - and crisis talks were held this week with their bid for fourth place and a Champions League berth looking very much in danger.
Juventus will be hoping for any slip up from Inter, knowing that they can close the gap to four points as they welcome Serie A strugglers Bologna to the Stadio Olimpico on Saturday night.
The Bianconeri put on a sterling performance in midweek but lost out to Chelsea 3-2 on aggregate and they will have to recover quickly with Bologna set to pose a tricky test.
Sinisa Mihajlovic's side might be 30 points behind Juve and just two points off the relegation zone, but they are fighting for their lives and defeated in-form Sampdoria 3-0 last weekend.
Roma face the greatest disappointment as they were eliminated 7-6 on penalties by Arsenal and Luciano Spalletti will have to rouse his injury-stricken side when they travel to Samp on Sunday afternoon bidding to snatch fourth spot from Fiorentina, who are just a point above them, and Genoa, in the standings.
AC Milan are currently in third place and a European hangover by Juventus and Inter could throw them right back into the title race if they beat 15th-placed Siena.
Napoli's trip to bottom side Reggina marks former Italy coach Roberto Donadoni's first time back in the dugout since the Azzurri's disappointing Euro 2008 campaign after he replaced the sacked Edy Reja this week.
Luigi De Canio also returns to work for the first time since the summer and he will be in charge of Lecce, who are only a place above Reggina, when they travel to Palermo.
Chievo occupy the other relegation spot, although they are level on points with Torino, and they face a tricky trip to Lazio who have pushed up the table following three victories on the trot. Toro travel to Atalanta.
Elsewhere on Sunday, Pasquale Marino's Udinese, who are the only remaining Italian club in Europe - in the UEFA Cup, welcome former club Catania while Cagliari play host to Genoa in Sardinia in Saturday's early game.