Belgian Lukaku, who cost United £75million, has not scored in his last eight games for Mourinho's team.
United's chief opted to go for Marcus Rashford against Everton and leave Lukaku on the bench.
Asked why by Sky Sports, Mourinho said: "The reason is he is playing lots of matches and lately, not just not scoring goals, but also not showing lots of confidence and sometimes we decide that the best thing for the players to be protected and away from the initial pressure."
Lukaku has nine goals this season in 17 games but five of those came in a Belgium shirt.
The former Everton striker has not scored for the Red Devils since a 2-1 win over Watford back in mid-September.
Mourinho is desperately in need of a win at Old Trafford.
His team has won just one game in their last seven in all competitions.
United sit 10th in the Premier League table and began the game against Everton one point behind the Toffees, with the chance to leapfrog them with a win.
Marco Silva's Everton, meanwhile, have won there last three consecutive Prem games.
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