Mata has scored two goals in four Premier League starts for United, including an excellent one in the 4-1 home victory over Premier League champions Leicester on Saturday.
"There are many players that we like but not all of them can come," Lopetegui told a news conference on Friday.
Mata, who missed out on Euro 2016, was named in Lopetegui's first squad but did not play in Spain's 2-0 win in Belgium and the 8-0 rout of Liechtenstein this month.
Lopetegui recalled Isco, despite the midfielder's limited playing time at Real Madrid.
"It's not the same being a sub at Real Madrid than at any other club," Lopetegui said.
"I can't deny that I like Isco. He has played 58 minutes in the league and that's very little. But he is a player that I like and that I trust."
West Ham goalkeeper Adrian and Chelsea defender Cesar Azpilicueta were dropped while Borussia Dortmund defender Marc Bartra was ruled out with a muscular injury.
There was no place for Chelsea midfielder Cesc Fabregas but Barcelona captain Andres Iniesta returned to the squad after missing the last two games with a knee injury.
Napoli forward Jose Callejon, who has scored five goals in six Serie A appearances, returns to the national fold after an
absence of almost two years.
Spain travel to Turin to face Italy, the team who eliminated them from Euro 2016 in the round of 16, on Oct. 6 before playing Albania four days later.
(Reporting by Adriana Garcia, editing by Ed Osmond)
