Rodrigo, Aymeric Laporte and Ferran Torres were all included in the starting XI in Seville, while Eric Garcia was named on the bench, but the three-time tournament winners were left frustrated, held to a goalless draw against Sweden.
Despite dominating throughout, Luis Enrique's side were left to rue missed chances and almost punished with two rare but glorious opportunities for the visitors.
Alexander Isak's effort was deflected onto the post by Marcos Llorente and Marcus Berg somehow scooped an Isak cross over the bar.
Sweden continued to thwart the home side, limiting the number of clear-cut chances in the second period.
Torres saw an effort blocked by Victor Lindelof in the City forward's last contribution before his substitution.
Despite late Spain pressure and six minutes of injury-time, the hosts could not find a way past Robin Olsen and Sweden hung on for a point.
Elsewhere in Group E, Slovakia earned a 2-1 win over Poland.
On Matchday Two, Sweden and Slovakia go head-to-head on 18 June (14:00) before Spain and Poland lock horns the following day (19 June, 20:00).
Group E will conclude on 23 June as Spain face Slovakia in Seville and Sweden face Poland in St Petersburg - both at 17:00 UK time.
Meanwhile, in England's group - Group D - today, Scotland were defeated by the Czech Republic at Hampden Park.