Argentina international Cambiasso, 32, and versatile Colombian Guarin, 26, both suffered leg injuries during the Coppa Italia semi-final defeat to Roma.
Statements published on the club's official website confirmed medical tests have discovered a muscle tear to Cambiasso's left adductor muscle while revealing a first-degree strain in Guarin's right calf.
The Nerazzurri have lost four of their last five Serie A games to fall nine points shy of the top three and the last Champions League place, with the absence of strikers Antonio Cassano, Rodrigo Palacio and Diego Milito proving particularly debilitating.
And Inter must now host mid-table Parma on Sunday without the South American duo - a first-choice pairing in midfield - who join Walter Gargano, Yuto Nagatomo, Cristian Chivu, Dejan Stankovic and Joel Obi on the sidelines. Luca Castellazzi, Ibrahim M'Baye and Gaby Mudingayi complete the list of absentees.
The latest injury news follows head coach Andrea Stramaccioni's criticism of reports suggesting he could lose his job before the end of the season.
"I do not give a damn about rumours about my future," he told inter.it. "As long as I'm on the Inter bench I will give 110 per cent for these colours."