The Old Lady have named former Italian national team manager Spalletti as their manager for the remainder of the campaign.
The experienced coach takes over from Igor Tudor, who was let go after the Serie A side's defeat by Lazio on Sunday.
Tudor had joined the club in March filling the shoes of Thiago Motta but departed after seven months after an eight-game winless streak.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 prior to assuming the Italy role, which missed out on the 2022 World Cup with Mancini at the helm.
Under his guidance, they made it to Euro 2024 exiting in the last 16 stage against Switzerland.
However, Spalletti was sacked by Italy in June post a qualifying defeat against Norway, putting Italy in danger of missing a third straight World Cup.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus in the midweek 3-1 triumph over Udinese moving them to seventh position in the league - trailing leaders Napoli by six points after nine matches.
Their Champions League campaign sees them in 25th place in the group stage, having lost once and drawn twice in their opening three matches.