The Monaco striker is a doubt for the competition in Brazil after sustaining damage to the anterior cruciate in his left knee during a Coupe de France tie in January.
While his club confirmed last month that the 28-year-old is in the second phase of his recovery, Colombia coach Jose Pekerman will need a contingency plan - especially after the former Atletico Madrid man played such a key role in their qualification campaign.
He registered nine goals in 13 appearances as Colombia finished second behind Argentina and Pekerman will now turn to the likes of Porto's Jackson Martinez, Hertha Berlin forward Adrian Ramos and River Plate's Teofilo Gutierrez to fill the void.
For Ramos in particular, a place at the World Cup would represent an impressive turnaround in the last 12 months, and the striker feels that the fight for a place in the squad for Brazil will be his "biggest challenge", particularly given that he was playing in the German second tier last season.
"It wasn't easy playing in the second division," Ramos, who is now the third highest scorer in the Bundesliga, told FIFA.com. "I never thought about going back to Colombia, but I did consider moving to another club. The first few months were tough, but I kept it to myself.
"Some of my colleagues are playing really well and there's a lot of competition. My dream is to be in Brazil, though. It's my biggest challenge and I just have to wait and see."
Tunisia have been out of action since failing to qualify for the World Cup - suffering a comprehensive 4-1 aggregate play-off defeat to Cameroon late last year, which saw former coach Ruud Krol leave his post soon after.
After a goalless draw in Rades, Tunisia capitulated in the return leg and interim coach Nizar Khanfir will now take charge of the first of their three friendlies over the course of the next few months.
Moez Ben Cherifia, Rami Jridi and Aymen Mathlouthi all miss out on the fixture in Barcelona due to their sides' involvement in African club competitions, but there is a return for Wahbi Khazri.
The Bastia midfielder missed both clashes with Cameroon amid a reported disagreement with Krol but makes a comeback as the sides meet for the first time since Colombia's win in World Cup 1998.
