Since the Villans won 3-0 in Switzerland on the opening matchday, captain John McGinn has succumbed to a hamstring injury, and the influential midfielder is set to miss his team's most high-profile game for many years.
Ross Barkley would be nearest to a like-for-like replacement, but Leon Bailey came into the starting XI against Ipswich Town last time out and may be retained on the hosts' right wing.
As Matty Cash is also ruled out, versatile England defender Ezri Konsa should continue to fill in at right-back, with Diego Carlos partnering Pau Torres in the centre; alternatively, young Lamare Bogarde could be trusted instead.
Bailey is back in the fold following a layoff, and the Jamaican forward - who registered 49 goal involvements in 119 Bundesliga appearances for Bayer Leverkusen, including three goals in nine games against Bayern - is one of several attacking options at Unai Emery's disposal.
Ollie Watkins will start up front, while super-sub Jhon Duran is poised to make an impact from the bench - the latter has already scored four goals as a substitute this season.
On his Champions League debut, Morgan Rogers created four chances versus Young Boys, and the England Under-21s star netted his first Premier League goal of the season at the weekend.
In addition to McGinn and Cash, long-term absentees Tyrone Mings and Boubacar Kamara are unavailable: both recently returned to training but neither is sufficiently match-fit to feature on Wednesday.
Aston Villa possible starting lineup: Martinez; Konsa, Carlos, Torres, Digne; Onana, Tielemans; Bailey, Rogers, Ramsey; Watkins