The veteran striker is set to have a fitness test in the lead-up to the match at Balaidos, where his absence would be a significant blow for the Sevilla-based high-fliers.
Castro has scored five goals in his past four games in all competitions, while his nine league strikes have helped Betis to sixth place in La Liga.
They can move up a further place on Monday night but Castro's injury represents a problem for Mel's attacking options with Joel Campbell and Juan Carlos also in doubt.
"We will wait before we make a small test for Castro," Mel told a press conference.
"I'm not sure if I will have to make changes. That will depend heavily on the participation of Joel, Juan Carlos and what we know after Reuben's test.
"They are all attacking players and we might have to look at some variations."
Mel did rule defender Jose Dorado out after he suffered an adductor problem in the midweek 1-1 Copa del Rey draw with Las Palmas.
"Dorado suffered his problem against Las Palmas and usually that injury takes around four weeks' recovery," he said.
With the injuries a concern, Mel is keen to make sure his side remain wary of the threat posed by Celta after they upset Real Madrid 2-1 in the Copa del Rey in midweek.
Chief on Mel's list of concerns is the form of striker Iago Aspas, who he believes is one of the best players in Spain at present.
"The nice thing with Aspas is that he is an unpredictable player," he said of the six-goal frontman.
"His goals have inspired the rise of Celta. He is one of the most important players in the competition."
Celta skipper Borja Oubina will have a late fitness test after he strained a hamstring in training on Saturday, while Alex Lopez (hamstring) and Samuel Llorca (knee) will miss out.