The Green Lions have not played for 18 days.
Both sides go into the tie having picked up a solitary point so far in the Isthmian South Central campaign, but the visitors have the benefit of having been in cup action while Guernsey have been left to take out their frustrations on the practice pitch.
The Green Lions have never beaten Leatherhead.
The Tanners have been kicking on in the cups, beating Dulwich Hamlet of the Isthmian Premier Division in an FA Cup first qualifying round replay, and also winning their FA Trophy first qualifying round tie against Hayes & Yeading United last weekend.
Tony Vance’s side are chasing a first win in 15 games, having last taken all three points in March.
That run includes a 4-1 defeat to Leatherhead on their last visit to Footes Lane, also the last meeting between the two sides.
The Surrey side finished third last season, losing to Marlow in the play-off final.
For Guernsey, Sam Murray is chasing a goal or two to take him level or past Ryan-Zico Black (24 goals) and to close the gap on Glyn Dyer (26). Tom Dodds will be unavailable for a few weeks due to an arm injury that forced him off against Harrow Borough. Ross Allen and club captain Jamie Dodd are recovering from injuries and will hope to be involved.
The game kicks off at 19:45 at Footes Lane.