The Brighton striker has returned to his club after not being fit enough for a place on the bench during Saturday's 2-2 draw against the Czech Republic.
Kenny Miller is suspended after being booked against the Czechs but manager Craig Levein has not called anyone else up.
Levein is also missing midfielder Scott Brown through suspension but full-back Steven Whittaker returns after a ban.
Charlie Adam is rated as doubtful after being forced off with 10 minutes left because of a hip injury.
However, Phil Bardsley looks set to recover from the calf problem that forced him off in the 75th minute, before the Czechs scored their first equaliser.
The loss of Miller and Mackail-Smith means Levein has just two realistic options for the lone striker role - David Goodwillie and Steven Naismith.
Blackburn striker Goodwillie was an unused substitute on Saturday and his only international appearance came as a 76th-minute replacement in the friendly win over the Faroe Islands last year.
Naismith played in midfield at the weekend but was short of his best after taking painkillers to overcome a hip problem, however the Rangers player has ample experience of playing up front at club level.
The likes of Barry Robson, James Forrest, Graham Dorrans and Robert Snodgrass could come in to bolster Levein's attacking options from midfield if Naismith is moved forward.
Levein must also assess the fitness of Alan Hutton and Darren Fletcher after their opening first-team games of the season, although the latter has declared himself ready to face Lithuania.
Levein also has Grant Hanley available if required after the Blackburn defender recovered from tonsilitis.