Apart from the League Cup, when coach Arsene Wenger has fielded a reserve team, Henry has been an ever-present in the Premier League and Champions League, scoring 20 goals in 27 games.
He will be replaced for the Highbury clash by Jose Antonio Reyes, who will be hoping to end a spell of injury and personal problems that have seen his season lose its way after a bright start.
Henry gets a breather after a gruelling year for club and country.
"From Jan 1, 2004 until the game against Manchester City (on Tuesday), Thierry played 56 games for Arsenal," Wenger told reporters on Friday.
"Add to that the qualifying for the 2004 European Championship, then the championship itself and one or two friendlies, and you get to 64, 65 games in one year."
Wenger said that his replacement, Reyes, was determined to recapture the sparkling early season form which brought him six goals in his first eight games including the Community Shield.
The Spaniard has scored only twice since then and has not played at all since a 2-2 draw with Chelsea on December 12. He subsequently spent some time in Spain on personal business.
"He needed a break, he had some private problems and then knee problems. Now he looks sharp, fit and ready to go again," Wenger said.
The coach did not elaborate on the 21-year-old's private difficulties.
"You never know how much it affects someone, because like all of us, there can be a difference between what we show and what kind of impact something has," Wenger said.
Reyes, who joined Arsenal from Sevilla in January last year, has also struggled to get used to the rough and tumble of English football and the physical punishment handed out by defenders.
"Every player takes some time to adapt," said the Frenchman. "He had a great start to the season and then a dip and I'm hopeful he'll start again. He's young and up front that's especially important...I think he will bounce back."
Sweden midfielder Fredrik Ljungberg and England defender Ashley Cole will also be rested, the latter being replaced by Frenchman Gael Clichy, while out-of-favour keeper Jens Lehmann will make a comeback in place of Spaniard Manuel Almunia.
"The challenge to him is to give Almunia tough competition," said Wenger, who has not picked the German since late November.
"They are close to each other and I feel at the moment Almunia is in front. But Jens is a fighter, he doesn't give up.
"You have to consider that you need two good keepers in a big club and that one of them will be unhappy."
Two months after agreeing the deal, 21-year-old Ivory Coast defender Emmanuel Eboue has completed his move from Belgian club Beveren and will be in the squad for Sunday's game.