Napoli were able to rest their star man and cruise to victory ahead of Liverpool’s visit in midweek.
Skipper Lorenzo Insigne, who scored the winner on the Reds’ last trip to the Stadio San Paolo, started the game against Sampdoria on the substitutes’ bench.
He was then introduced for a run-out 15 minutes from time.
That was after Dries Mertens’ had bagged a double to put Carlo Ancelotti’s men in control.
The victory lifted Napoli, who opened the campaign with a 4-3 win against Fiorentina before losing to Juventus by the same scoreline, to fourth place.
Both teams, then, will move into the Group E opener off the back of fairly comfortable two-goal wins, though Liverpool had to do slightly more work.
The hosts’ first clean sheet of the season will be a welcome boost after shipping seven in two matches, but keeping out Mohamed Salah, Roberto Firmino and Sadio Mane is one of the toughest challenges in football.