The Barcelona and Argentina man believes his teammate needs to think only of himself as he starts his recovery from a hamstring injury.
The star forward is currently facing six to eight weeks out of action with a hamstring injury, which he picked up against Betis last weekend.
Mascherano, who captained Argentina in the draw with Ecuador in the absence of Messi, admits he knew the injury was a serious one and urged his club and international teammate to focus only on himself as he works his way back to fitness.
"When Messi was lying on the ground and looking back to the bench I knew something was badly wrong,” the former Liverpool player said to Ole. “Now he has to be the most selfish person in the world. I say that in a good way - he needs to really look after himself and recover well.
“An injury is never good news but it certainly does not hurt to rest properly and take some time out just for you. He needs to focus on recovering.”
Mascherano rejected the suggestion that being without Messi could prove to be a positive experience for Barcelona as the club's learn to reduce its dependence on him.
“Not having Messi in the team is never a positive thing,” he said. “Leo is fine now. He has passed the stage of logical bitterness that you get when you are injured and is now focused on getting better. It is just a muscle injury, so nothing too severe.”
Barcelona faces Granada on Saturday when it returns to action after the international break, a match which is followed by a Champions League trip to Ajax.