Robert Moreno's side guaranteed their place at next year's finals with a 7-0 win over Malta earlier this week, while Romania's hopes of reaching successive European Championships took a significant blow following a 2-0 defeat to Sweden on Thursday.
Spanish football was rocked earlier this year by news of Luis Enrique's daughter passing away, two months after the former Barcelona star resigned from the role of national coach to focus on family matters.
The arrival of Moreno over the summer has added to the sense that this team remains in a period of instability, having gone through three different managers since June 2018.
Indeed, a pair of draws away at Norway and Sweden last month, which saw Spain concede and then score injury-time winners respectively, indicates that this is a team currently lacking a sense of assurance when it comes to game management.
What this team does not lack, however, is a wealth of young talent at its disposal, with the likes of Mikel Oyarzabal, Dani Olmo and Pau Torres all demonstrating a capacity to succeed on the international stage.
With this game against Romania not bringing any serious pressure, Moreno may end up handing the aforementioned youngsters further chances to impress as Spain prepares for Euro 2020.
For Romania, however, there is a strong sense of uncertainty over the future following a disappointing end to what started off as a promising Euro 2020 qualifying campaign.
Having won four of their last seven games ahead of facing Sweden, Cosmin Contra's side knew that a home win would have taken them ahead of Sweden into second place ahead of their final group game.
As it was, Romania produced a lacklustre performance in front of their own fans, failing to mount an adequate response to going 2-0 down after 35 minutes.
Moreover, the game was temporarily halted by the referee when Real Sociedad striker Alexander Isak was subjected to racist abuse after being introduced with 12 minutes to go in Bucharest, leaving a bad taste that has become far too familiar in Europe this season.
It is against this sad backdrop that Romania must travel to Madrid knowing that they will need other results to go their way if they are to qualify for Euro 2020 as one of the best third-placed teams.
Recent Spain form: WWWDDW
Recent Romania form: WLWWDL
For Romania, Denis Alibec looks likely to start the game after the forward demonstrated some bright moments during a 15-minute cameo against Sweden.
Spain possible starting lineup:
De Gea; Carvajal, Torres, Ramos, Gaya; Busquets, Thiago, Niguez; Oyarzabal, Alcacer, Olmo
Romania possible starting lineup:
Tatarusanu; Mogos, Rus, Nedelcearu, Bancu; Deac, Baluta, Hagi, Mitrita; Puscas, Alibec
We say: Spain 3-0 Romania
Romania will certainly put up a good fight against a team with a few fresh faces, but the visitors might lack an element of bite in the final third, which is likely to pave the way for Spain to dominate the game and score a few goals.