Italian striker Federico Macheda was sent out on loan from Manchester United for the first time when he returned to Sampdoria during the winter transfer window in 2011. He returned to his native Italy to sign for Sampdoria as a Manchester United loanee on January 8, 2011. Macheda had been signed from Italian team Lazio as a teenager some years earlier.

Federico Macheda spent the second half of the 2010/11 season at Sampdoria as he was seen as the replacement for compatriot Antonio Cassano who left the club for AC Milan. He made his Sampdoria debut during the 2-1 home victory over AS Roma in the league encounter played on January 9, 2011. Macheda featured against Roma around a day after his transfer was confirmed.

Macheda scored his first goal for Sampdoriaon his first start as he opened the scoring during the Coppa Italia tie with Udinese in a game which ended in a 2-2 draw. Sampdoria went on to progress to the next stage of the competition by beating their opponents 5-4 on penalty. It was his only goal for Sampdoria during his time at the club as a Manchester United loanee. He was unable to save Sampdoria from relegation to the Italian Serie B during his time at the club  Federico Macheda could make a return to Sampdoria in the new season (2011/12 season) as revealed by his agent, but the player was adamant that he wants to stay at Manchester United. In the end, he got his wish as he stayed with the Red Devils for the first half of the 2011/12 season before being loaned out to London team Queens Park Rangers (QPR).

Federico Machedascored just once in 14 appearances during his loan spell at Sampdoria. He had an unsuccessful loan spell at the club.