La Roja have already booked their spot in next summer's finals having collected 20 points from their eight matches, while Malta are bottom of the section with just three points to show from their eight fixtures.
Six wins, two draws and zero defeats - that is how Spain have performed in Group F. In truth, they have not needed to break a sweat to book their spot in the finals of Euro 2020, although Robert Moreno's side will enter this match off the back of successive draws.
Indeed, the 2010 world champions followed a 1-1 draw in Norway on October 12 with another 1-1 draw in Sweden three days later. Six straight wins at the start of their campaign placed them in a very strong position, though, and they will be the overwhelming favourites to overcome Malta on Friday night.
For a team that were so dominant not too long ago, it would be fair to say that it has been a disappointing few years for La Roja at international level. Indeed, they were eliminated in the group stages of the 2014 World Cup before falling at the last-16 stage in Russia last summer.
Spain were knocked out of the last European Championships in the round of 16, although it is worth considering that they have won the competition in two of their last three participations. One thing is for sure - Moreno's side cannot be written off ahead of next summer due to the talent that they can call upon.
Malta have competed in every qualifier for the European Championships and World Cup but have never managed to make it to the finals of any major international competition.
It was always going to be difficult for Ray Farrugia's side to compete in this section, and they are currently bottom of Group F with just three points to show from their eight matches. Their sole win arrived against the Faroe Islands back in March, which proved to be their first competitive victory on home soil for almost 13 years.
Indeed, not since a 2-1 success against Hungary in October 2006 had the Reds managed to triumph in a competitive fixture on their own patch and they can at least take that from this campaign if nothing else.
Both Romania and Sweden have put four goals past them in separate matches, but the 1-0 defeat away to the Faroe Islands in the middle of last month will go down as their poorest result in the group.
Friday's encounter will be the ninth time that these two teams have locked horns in international football; Malta have only scored once, which came during a 12-1 defeat back in December 1983. Not too many are expecting a miracle from the visitors this week, but Spain do not have much to play for in Cadiz.
Spain form: WWWWDD
Malta form: LLLLLL
Wolverhampton Wanderers attacker Adama Traore had been set to feature for Spain having been called up to the senior squad for the first time, but the former Barcelona youngster had to withdraw due to an injury.
It seems likely that the skipper Sergio Ramos will start, while there is expected to be a spot in the middle of the park for the supremely talented Fabian Ruiz, who continues to be linked with Real Madrid and Barcelona.
Colchester United's Luke Gambin is also expected to win his 23rd cap for the Reds in a wide area.
Mifsud has 41 goals for Malta but no other player has managed more than four, which is an indication of the troubles facing the away side on Friday night.
Spain possible starting lineup: Arrizabalaga; Navas, Ramos, Pau Torres, Gaya; Cazorla, Rodri, Fabian; Oyarzabal, Morata, Olmo
Malta possible starting lineup: Bonello; Z Muscat, Caruana, Agius, Mbong; Corbalan, Vella, R Muscat, Gambin; Mifsud, Nwoko
We say: Spain 4-0 Malta
It is difficult to back anything other than a home win on Friday night. Spain's team is expected to be much changed, but La Roja have not lost a World Cup or European qualifier since October 2014. Malta, meanwhile, have been beaten in their last seven matches without scoring and will struggle again here.