The setbacks both occurred during the first half of the match at the Stadio Olimpico this evening.
Kumbulla lasted only 15 minutes before having to limp off, as he was caught by Olivier Giroud in an accidental collision.
At first, it seemed to only be a bruise to the thigh just above the knee, but now Sky Sport Italia report that the centre-back has been diagnosed with a torn anterior cruciate ligament in his right knee.
That means the season is practically over for the Albania international.
As for Belotti, he had breathing difficulties after a knock to the ribs just before half-time and was ready to come back out for the restart.
However, in climbing the stairs back up from the locker room to the pitch, Il Gallo realised he was struggling to breathe and asked to be replaced by Stephan El Shaarawy.
It is reported that Belotti has sustained a fracture of the cartilage around his rib.