La Roja are currently top of the section with seven points, two points clear of second-placed Germany, and they will enter the match off the back of a 1-0 win over Switzerland on Saturday.
Ukraine are currently third in Group 4, collecting three points from their three matches in the section against Switzerland, Spain and Germany.
Andriy Shevchenko's side opened their 2020-21 UEFA Nations League campaign with a 2-1 home victory over Switzerland but have lost their last two against Spain and Germany.
Ukraine also suffered a 7-1 defeat to France in an international friendly last week, but it must be noted that the Yellow and Blues are far from at full strength after a coronavirus outbreak.
Taras Stepanenko was among those unavailable to travel due to a positive coronavirus test, while Mykola Matviyenko, Andriy Pyatov and Junior Moraes were also forced to withdraw after the rest of the Shakhtar Donetsk squad were placed into isolation.
Ukraine actually finished ahead of Portugal in their Euro 2020 qualifying section, remaining unbeaten across eight matches, collecting an impressive 20 points in the process, and they will mainly be using the Nations League to prepare for next summer's tournament.
Spain, meanwhile, will enter the match off the back of a 1-0 win over Switzerland on Saturday, with Mikel Oyarzabal scoring the only goal of the contest on home soil.
Luis Enrique's side opened their 2020-21 Nations League campaign with a 1-1 draw with Germany before beating Ukraine 4-0 in their first home game of the competition on September 6.
La Roja will now be looking to make it successive victories in the tournament ahead of clashes away to Switzerland and at home to Germany in November.
Spain breezed through their qualification section for next summer's European Championships, winning nine of their 10 matches, while they are now unbeaten in all competitions since losing to Croatia in the 2018-19 edition of the Nations League, a run which stretches 15 matches.
Ukraine have actually never beaten Spain in an international game, with La Roja winning five of their six previous meetings, including a 4-0 success in the reverse clash on September 6.
Ukraine Nations League form: WWLWLL
Ukraine form (all competitions): WDWLLL
Spain Nations League form: WLLDWW
Spain form (all competitions): WWDWDW
As mentioned, Ukraine are far from at full strength due to a coronavirus outbreak, meaning that it will once again have to be an experimental XI for the home side on Tuesday night.
In addition to those absent due to coronavirus restrictions, neither Manchester City's Oleksandr Zinchenko nor Shakhtar's Yevhen Konoplyanka are in the squad due to injury, but West Ham United's Andriy Yarmolenko is a part of the current selection and should once again feature in an attacking position for Shevchenko's team.
The back five could remain unchanged, meaning that Sergi Roberto and Sergio Reguilon could start on the bench once again, but Ceballos has a chance of featuring alongside Mikel Merino and Sergio Busquets in midfield.
Enrique has altered his attack on a number of occasions in recent games, and it could be Dani Olmo's turn to drop out, with Ansu Fati and Oyarzabal potentially joining Gerard Moreno in the final third.
Adama Traore again featured off the bench against Switzerland, and the Wolverhampton Wanderers attacker is likely to be among the substitutes for a third game in succession.
Ukraine possible starting lineup:
Bushchan; Karavaev, Zabarnyi, Mykolenko, Sobol; Yarmolenko, Malinovskyi, Sydorchuk, Kovalenko, Tsygankov; Yaremchuk
Spain possible starting lineup:
De Gea; Navas, Ramos, Torres, Gaya; Merino, Busquets, Ceballos; Fati, Gerard Moreno, Oyarzabal
We say: Ukraine 1-2 Spain
Ukraine performed impressively against Germany on Saturday despite suffering another defeat, while it would be fair to say that Spain are still searching for their best form. We are expecting a tight game in Kiev but believe that the visitors will have enough quality to pick up another three points.