Everton boss Roberto Martinez said the festive fixtures are "pivotal" for his side following the 1-0 home defeat by Stoke City.
Injuries to defenders Phil Jagielka and John Stones, goalkeeper Tim Howard and winger Kevin Mirallas added to a suspension for Steven Naismith ahead of Sunday's trip to Newcastle.
"Everything that could go against us, did," the Spaniard told BBC Sport.
"It is a pivotal moment in the season for us."
Everton are 13 points behind where they were last season after 18 games, when they went into the Boxing Day fixture in fourth spot.
It is the first time the Goodison Park club have suffered back-to-back league defeats this campaign.
Martinez said: "I don't think we are in a great moment of the season but I don't think anything that could have gone in our favour did today."
Howard pulled a calf muscle and had to be helped from the pitch at half-time. Jagielka also failed to re-appear for the second half after landing awkwardly and stretching his right ankle ligaments.
Martinez said both were likely to miss Sunday's game, and there are doubts over the fitness of 20-year-old centre-half Stones and Belgian winger Mirallas.
Both had only returned to the Toffees' XI on Friday after injury - Stones last played in October when he injured his ankle at Manchester United, while Mirallas missed the 3-0 loss to Southampton with a minor knock.
The mounting injury list leaves Martinez counting the cost of his side's fourth loss in the last six league games.
He added: "The challenge on Kevin meant he was fortunate to finish the game. John Stones picked up a knock on the same ankle that he injured earlier in the season. He did very well to finish the game."