The Nigerian international scored in the first half but the Uruguayan equalised in the dying minutes of the game. The Isolani were missing Joao Pedro in attack and Razvan Marin in midfield but welcomed back Alessio Cragno in goal.
Napoli took the lead after 13 minutes. Diego Demme intercepted a Cagliari throw, he then found Lorenzo Insigne, and the Neapolitan captain lobbed the ball to Osimhen, who controlled the ball with his right foot and beat Cragno with the left.
Cagliari came close to equalising when Leonardo Pavoletti could not get his header on target, and then the ball fell to Gabriele Zappa, who hit the post.
Hirving Lozano squandered a great chance to double Napoli’s lead when he failed to direct Osimhen’s cross on target. Partenopei goalkeeper Alex Meret was alert towards the end of the first half, saving a Pavoletti header and then reacting quickly to prevent Nahitan Nandez from scoring the rebound.
Osimhen should have made it 2-0 three minutes into the second half but his header just missed the goal while Piotr Zielinski forced a save out of Cragno and Demme had a shot that hit the post. Osimhen also had a goal disallowed after he was adjudged to have fouled Cagliari defender Diego Godin.
Isolani wing-back Charalampos Lykogiannis had a rare chance with a header at the far post but it went wide and the Neapolitans had chances to extend their lead.
An Osimhen shot flashed across goal, Giovanni Di Lorenzo beat three opponents but his shot was deflected away, and then Insigne shot straight at Cragno. Meret had to be attentive too, making an amazing save from a Pavoletti volley.
Two minutes into stoppage time, Alfred Duncan found Nandez at the far post, who stuck his leg out to deflect the ball into the net.
Napoli go up to 67 points after 34 matches in Serie A whereas Cagliari now have 32.