The Royal Spanish Football Federation (RFEF) confirmed earlier on Tuesday that Luis Enrique will be absent for the clash and that his assistant Robert Moreno will lead the team instead.
La Roja face Malta in Ta' Qali three days after they began their group with a 2-1 home victory over Norway.
Captain Ramos, who scored the winning goal in that game, has sent his best wishes to Luis Enrique and says that they hope to deliver another three points for the 48-year-old.
"Mister, we are sorry for the news," the Real Madrid defender posted on Twitter. "We hope that everything goes as well as possible. You know that the team is with you to the death and today we will get a good victory.
"The family is sacred. We'll win for you. A lot of strength and encouragement. Big hug."
Míster, sentimos muchísimo la noticia. Esperamos que todo salga lo mejor posible. Que sepas que el equipo está contigo a muerte y hoy dará la cara para conseguir una buena victoria. La familia es sagrada. Ganaremos también por vosotros. Mucha fuerza y ánimo. Fuerte abrazo.— Sergio Ramos (@SergioRamos) 26 March 2019
Spain began 2019 positively in Valencia on Saturday, and were 1-0 up within 20 minutes against Norway, through Rodrigo.
While the visitors did pull one back, Enrique’s side earned all three points though Ramos’ late penalty.
La Roja will be hoping to put the last 12 months behind them as they begin their Euro 2020 qualification campaign. After the fiasco surrounding Julen Lopetegui before the World Cup in 2018, Spain suffered the embarrassment of crashing out to Russia in the last-16 stage of the tournament.
They also endured an indifferent Nations League campaign, and despite winning at Wembley and trashing Croatia 6-0 in their opening two games, Spain ultimately finished second to Gareth Southgate’s England.
The former World champions have been drawn in a Euro 2020 qualification group that includes Sweden, Norway, Romania and the Faroe Islands.
With experienced heads such as Ramos, David de Gea, Jordi Alba and Sergio Busquets, they are still among the favourites to win the tournament next year.
Spain even host four matches of Euro 2020, with the city of Bilbao selected as one of the ten cities to stage games.