The contest at Goodison Park comes less than three days after Spurs' 3-1 Europa League victory over Panathinaikos on Thursday night, for which Villas-Boas fielded a relatively strong starting XI.
Asked if he thought fatigue might be an issue for Tottenham, Moyes said: "I think if we had been playing, I would be thinking about that - I'd be saying it is a possibility."
He added: "Does that really happen? I'm not sure. I'm not a great believer that it really happens. But if I was the manager, I would certainly be worried about it."
It has come as little surprise to Moyes to see Tottenham beginning to find their feet under Villas-Boas. "They have a really good team," Moyes said.
"It always takes managers time to settle in, but when you are left with an array of players like Tottenham have got, then you are always going to be very close to the top of the league."
Moyes says forward Mirallas, who has missed four games due to a hamstring injury, and full-back Coleman, sidelined for three by an unspecified problem, have "outside chances" of featuring against Spurs. Victor Anichebe (hamstring) and Phil Neville (knee) remain on the casualty list.
Meanwhile, Villas-Boas has revealed his deep respect for Everton boss David Moyes as he prepares to do battle with the Scot. "He has done tremendously well," the Tottenham manager said. "He has changed the mentality of the club. They went through incredibly difficult situations financially and has always built strong teams."
Villas-Boas looks set to recall Hugo Lloris in goal after giving Brad Friedel a run out in Tottenham's Europa League win over Panathinaikos on Thursday.
Gareth Bale is unavailable due to a hamstring injury and Michael Dawson also looks unlikely to play due to a similar concern. Dempsey will probably start in Bale's place on the left, leaving Adebayor and Defoe free to resume their partnership up front.
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