Fletcher and Melksham were the only injury concerns out of the Dons' camp after their comfortable Dreamtime at the 'G victory over Richmond on Saturday night.
Veteran defender Fletcher left the ground with a back injury in the final quarter, while NAB AFL Rising Star nominee Melksham missed a lengthy chunk of the match after hurting his ankle.
"We had a few sore boys in the last 15 or 20 minutes, when we took Fletcher off and he had a slight inconvenience with his back," Knights said after the match.
"He should be fine," he added.
Melksham returned to play a late spell in the midfield with his ankle strapped, but Knights said he was no walk-up start for Friday's game. A win over the Bulldogs could see Essendon square its season ledger at five wins and five losses, after recording back-to-back victories for the first time this year.
"Jake Melksham was obviously really courageous with what he did to go back on," Knights said.
"Ankles can tend to be a little bit tedious ... so we'll know more in the next 48 hours. I would have thought he was possibly in some doubt for Friday considering it's a six-day turnaround."
Fletcher, 35, played his 321st match for the Bombers, passing club great Dick Reynolds to move into second on the all-time list at Windy Hill - behind only Simon Madden.
Knights praised his containing job on Jack Riewoldt, who kicked four of his six goals with the game well lost.
"He was just getting away a little bit ... Dustin went onto him and did a sterling job," Knights said.
"That's the great thing about Dustin - he's got the speed to come up on the lead and the great ability to go back with courage with the flight of the ball.
"Those long arms make it really difficult for forwards. They have for many a year and they will continue for many a year because his speed and his reach make him a difficult match-up as a defender.
"[But] our defence has to understand that at some stage we are going to be without him."
