The Old Lady have named ex- Italian national team head coach Spalletti to take the helm for the rest of the term.
Spalletti steps in for Igor Tudor, who was let go following the loss to Lazio last weekend.
Tudor arrived at the club in March to replace Thiago Motta but exited following a seven-month stint following a string of eight matches without a victory.
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.
He secured their spot in Euro 2024 but were eliminated in the round of 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June after a World Cup qualifying defeat by Norway, with the Azzurri at risk of missing out on a third consecutive World Cup.
Spalletti has also managed Inter Milan, Roma and Udinese in Serie A and secured two Russian Premier League titles with Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus for their 3-1 win against Udinese on Wednesday which left them seventh in Serie A - six points adrift of Napoli at the top after nine rounds.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.
