Mel will replace Gaizka Garitano from Thursday when Deportivo hosts Atletico Madrid at the Riazor stadium, reports Efe.
Garitano led the team in a run of defeats, the last on Saturday, when the team incurred its fourth straight loss against Leganes.
Currently Deportivo holds 17th position in La Liga, just two points away from the relegation zone.
Pepe Mel takes the job in an attempt to give a hand to a team wanting to stay in the Primera Division next season.
Mel last trained Real Betis in 2014-16, but was sacked in January 2016 with his team in 15th place, following a poor run and he has not trained any other team since then.