Spurs prepare to play Tromso in the Europa League on Thursday, Cardiff City in the Premier League on Sunday and Aston Villa in the Capital One Cup on Tuesday, all within six days of each other.
With other Capital One Cup games due to be played on Wednesday, the Portuguese "can't understand" why his side would be forced into an even more difficult fixture list than they already faced.
"How can a game be scheduled after two days, immediately putting the players' careers at risk and the risk of injuries?" Villas-Boas fumed to reporters.
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"So this amount of fixtures forces us to make some changes in the team but we take the competition very, very seriously and we will be very, very strong."
But the Football League argues that it had no other choice with its fixture planning as two of Villa's local rivals are set to host matches on Wednesday against other Premier League clubs, who also play on Sunday - Birmingham City will host Swansea City, while West Brom welcome Arsenal to the Hawthorns.
"There is a fixture congestion issue caused by three Midlands clubs being at home to sides playing on Sunday in the Premier League," a Football League spokesman explained.
"In an ideal world, all three games would be played on the Wednesday night but, for crowd safety reasons, it is not possible."