Messi is widely considered one of the greatest players of all time, but his detractors often point to the fact he has never won international football's biggest trophy in order to rule out his eligibility as the best ever.
Messi scored four goals at the 2014 World Cup, but ultimately fell short of adding the trophy to his extensive list of team and individual honours.
Winfrey has been labelled the most influential woman in the world, with a net worth of over $2.8 billion, and was asked on Argentine television to give Messi an inspiring message to help him bring the World Cup back to Argentina.
The 64-year-old urged the Barcelona superstar to find his inner strength to achieve his biggest feat to date, telling Pronto: "Messi this message is for you, and it's something you already have to know in advance.
"You have to go deep, deep inside of you to find all the strength you have inside. Messi, be a warrior."
Winfrey's co-star in new film A Wrinkle in Time, Reese Witherspoon, also admitted a fondness for the 30-year-old, revealing that her son is a huge fan.
"Messi is my son's favourite player, he has all his jerseys and everything," Witherspoon said (Goal.com)(MSN Sports)