The Giallorossi lost at the Sardegna Arena despite goals from Carles Perez and Federico Fazio, as Charalampos Lykogiannis, Razvan Marin and Joao Pedro all got themselves on the scoresheet.
It was Perez who cancelled out Lykogiannis's fourth-minute opener midway through the first half, only for Marin and Pedro to both find the net shortly after the restart.
Fazio's header then set up a 20-minute search for an equalising goal for Paulo Fonseca's side but unfortunately one would not be forthcoming.
Roma are back in action on Thursday: they travel to England to face Manchester United in the first leg of their Europa League semi-final.
CAGLIARI 3-2 ROMA
GOALSCORERS: Lykogiannis (4'), Marin (57'), Joao Pedro (64'); Perez (27'), Fazio (69')
CAGLIARI (3-4-1-2): Vicario; Godin; Ceppitelli, Carboni; Nandez, Marin (Duncan), Deiola, Lykogiannis (Zappa); Joao Pedro; Pavoletti (Cerri), Simeone (Rugani)
Unused subs: Aresti, Ciocci, Klavan, Calabresi, Asamoah, Walukiewicz
ROMA (3-4-2-1): Pau Lopez; Mancini, Smalling (Cristante), Fazio; Santon (Karsdorp), Villar, Diawara (Veretout), Peres (Spinazzola); Perez, Pellegrini (Mkhitaryan); Mayoral
Unused subs: Fuzato, Jesus, Dzeko, Reynolds, Kumbulla, Pastore, El Shaarawy
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