Ireland face Scotland in a Euro 2016 qualifying encounter on Friday, before hosting USA in a friendly on Tuesday.
Having met up with the squad ahead of Friday's clash in Glasgow, McCarthy and Whelan have now returned to their clubs to recover from hamstring and leg injuries respectively.
Everton's McCarthy had been struggling with his issue ahead of the international break, while Whelan was a surprise inclusion in Martin O'Neill's squad having not played since mid-October due to a fractured leg.
Although he has been able to train, Whelan is not ready for a return to competitive football, and the 30-year-old will now head back to Stoke City to continue his rehabilitation.
Ireland sit second in Group D, behind Poland on goal difference after three qualification matches, and Friday's trip to Glasgow represents a chance to extend their advantage over Scotland to six points.
The latest withdrawals come as an added blow to O'Neill, who lost Stoke's Marc Wilson to a hamstring injury prior to the international break.
