Last week, Rune withdrew from the first round of the Masters 1000 tournament in Monte Carlo after suffering from a bad stomach, and in general, the Dane has not played much tennis in the past month as illness has haunted his season so far.
In Barcelona, Rune is seeded six and could end up facing Casper Ruud, who is seeded number two, in the quarter-finals of the tournament.
However, if he is get that far in the tournament, he will surely have to produce another level of tennis than what was the case in the early parts of the game against Albert Ramos-Vinolas.
Rune seemed short of match practise and struggled to get his game plan going against the Spaniard, who failed to take advantage of two break points, when he was ahead 3-2 in the first set.
But gradually it became evident that the 37-year old Ramos-Viñolas, who has dropped to 234 in the world rankings is far from the level he displayed, when he enjoyed his career-high ranking as no 17 in May 2017.
The Spaniard made several crucial errors, when he was broken at 5-5 in the first set and Rune secured the set with a strong backhand winner in his own service game.
Rune carried the momentum into the second set, where he immediately broke Ramos-Viñolas' serve again.
Ramos-Viñolas did manage to fight back to level the score at 3-3 but from then on Rune tightened his grip on the match, while Ramos-Viñolas produced more and more unforced errors.
Rune closed out the match with a powerful smash in his own service game and the Dane is now set to face the winner of Sebastian Baez and Damir Dzumhur in the next round of the tournament.