On 9 March 2009 De Canio signed a contract to become head coach of Serie A relegation battlers Lecce, replacing Mario Beretta at the helm of the "salentini", but did not manage to save the side from relegation. On 31 May 2009 US Lecce announced De Canio had refused to extend his contract with the club; however, on 6 June the club officially confirmed to have reached an agreement with the former QPR manager, who guided the "giallorossi" back to the top flight, as league runners-up, in their 2009–10 Serie B campaign. He was sacked on 22 May 2011 as Lecce finished 17th at the end of the 2010–11 season.