A converted penalty by Locatelli and a late goal from Lopez brought a clean win.
Napoli hosted Sassuolo in the sixth round of the Italian Serie A.
Gennaro Gattuso's charges failed to realize their chances, which cost them a positive result.
After Locatelli's goal from the penalty spot, Napoli desperately tried to recoup, and at the end of the fight he could have saved at least a draw for himself, but Manolas's goal was canceled due to offside.
Instead, Maxi Lopez increased Sassuolo's advantage already in compensated time for the second half, and the final whistle recorded Napoli's home defeat with a score of 0: 2.
Napoli - Sassuolo 0: 2 Goal: Locatelli, 58 (pen), Lopez, 90 + 5 Napoli: Ospina - Di Lorenzo, Coulibaly, Manolas, Hisay (Mario Rui, 70) - Bakayoko, Fabian Ruiz, Mertens (Elmaz, 70).
Sassuolo: Consigli - Ayhan, Ferrari, Chirikesh (Burabia, 90 + 1), Rogerio - Lopez, Locatelli, Traore (Defrel, 68) - Mulduur (Karyopoulos, 81), Raspadori (Marlon, 88), Boga (Obiang, 81).
Warnings: Manolas, Ospina - Locatelli, Burabia.