Midfielder Downes hobbled off the field during their 1-0 defeat at Manchester City on Saturday while Yukinari Sugawara went unused.
Martin avoided risking the Japan international after he was not passed fit to start against the reigning Premier League champions.
He instead turned to James Bree, handing the former Luton Town defender his first league appearance of the season.
Saints also withdrew Tyler Dibling at half-time, with Martin citing the teenager’s fitness as the primary reason.
He told the Daily Echo: “(Bringing) Tyler (off) was tactical. He looked knackered. We spoke about this on Thursday.
He’s an 18 year old lad. The level of intensity has gone through the roof for him compared to what he’s used to.
“He’s playing against the best team in Europe and it just wasn’t quite his day. Defensively, we needed a bit more help with Adam, who knows and understands the game a bit more.
“We also felt Adam’s runs in behind (would help) because he’s one of the best at it. We felt it could really hurt them and it did on a few occasions.
“Flynn just seems a bit battered and bruised. I thought he was great today. The Flynn that we know and love was really, really back.
“So many of them played with a spring in their step and big courage today, which I love.
“Taylor Harwood-Bellis was fantastic. Kyle on the right was really brilliant. So, yes, they need to live there now. But hopefully, all three will be fine for Tuesday.”
Saints will also be without former Stoke City loanee Will Smallbone and Scottish forward Ross Stewart for Tuesday evening’s game.
Goalkeeper Gavin Bazunu remains out with a long-term injury while Kamaldeen Sulemana is only fit for up to 20 minutes of action.
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