Arsene Wenger is expected to rotate his squad, with the likes of Alex Oxalde-Chamberlain returning to the starting line-up, but face a League One averaging over two goals a game
Without a trophy since the club's 2005 success in the same competition, Arsene Wenger's men are likely to have too much for a Coventry side which is fighting for promotion from the third tier despite a 10-point deduction.
Much credit has gone to Arsenal's attacking players this season - seven different players have scored in those six wins - but no side has a better defensive record in England's top flight with just 19 conceded.
While Abou Diaby (knee) is also a long-term absentee, better injury news sees returns for Thomas Vermaelen (knee), Nicklas Bendtner (ankle), Aaron Ramsey (thigh) and Mikel Arteta (calf) quickly approaching.
Arsenal has a rich history in the FA Cup, having won the competition on 10 occasions. Only Manchester United has won the tournament more times, and Coventry is also a former winner, in 1987.
Free-scoring Coventry is unbeaten in six matches and sits 11th in the table, just eight points off the playoff places in England's third tier, despite the penalty handed down to the club in preseason.
Leyton Orient is the only side with more League One goals than Steven Pressley's charges – who have netted 55 in 26 matches – and in Leon Clarke, they have the division's top scorer with 15.
Clarke has handed a transfer request in amid interest from Wolves, though.
The two sides met in the third round of the Capital One Cup in 2012, with Arsenal romping to a 6-1 home win in a match that saw Olivier Giroud score his first goal for the club.
This clash will just be their fourth against each other in the FA Cup. Arsenal knocked Coventry out of the competition in the fourth round in 1975 and 1977, and 37 years on, they will hope for the same result in their continued push for trophies.