Mourinho can name up to 12 substitutes in the Europa League but just seven in the Premier League – and nine senior players, including Dele Alli, missed out on a place in the 18 for Monday's 1-0 win over Burnley.
A number of those, including Alli, Serge Aurier, Harry Winks and Davinson Sanchez, are expected to feature in Belgium, while Gareth Bale will definitely start after Mourinho claimed the forward is nearly back to peak condition.
Tottenham's squad is so strong, Mourinho was able to leave Eric Dier and Tanguy Ndombele in London as a precaution but the Portuguese says every one of his players deserves to be involved.
"I'll change [my team tonight] because my squad allows me to do it," Mourinho said. "It's not a change of eleven players, it's a mixture.
"Every time I don't play a player, especially this season with the way everybody is working, I feel very hurt. I feel very sorry because everybody is working hard to play. It's going to be that way but Tottenham with a very strong team.
"Sometimes the players make our choices easy when they don't work hard," Mourinho added. "But these boys – all of them – are making my life easy [because] I have everybody available and in conditions to play.
"But they are making my life difficult because then every time I have to make a selection, it hurts me.
"In the Premier League, with only a small bench you leave lots of people behind and I have to confess that hurts me deeply.
"Sometimes I feel that decisions are unfair to some players and that is hard. We work all together, the group is really a strong one where everyone wants to give what he can to the team.
"And then to select players and teams and to leave people out is really a bad feeling."
Harry Kane and Heung-min Son, who have begun the campaign in remarkable form, are expected to be rested against Antwerp but Mourinho has warned the Belgians that Bale is close to being fully up to speed, having returned to Spurs from Real Madrid with an injury last month.
"We all have not just the feeling, but also the data, that Bale is arriving," Mourinho said. "He is working very hard. He is a great example for everybody.
"His behaviour as a team guy is incredible, his behaviour as a Tottenham man is remarkable and he is coming. I can see just with my eyes but then the scientific data is also [that he is] coming. I think tonight we can see Gareth at a good level and hopefully he can fly."
Spurs are also without Japhet Tanganga (thigh), while Paulo Gazzaniga, Joe Rodon, Danny Rose and Gedson Fernandes are ineligible.
The game will be played behind closed doors after Belgian authorities reinstated the ban on supporters but Mourinho insists he feels safe during European away games, despite the rising infection rates across the continent.
"I believe that national teams are the space where even with great organisation lots of travelling and players travelling separately is more dangerous," he said.
"But at a club level, honestly I feel safe."
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