The Argentina captain was left clutching his lower back after being accidentally kneed by an onrushing Honduran, having tumbled over midway through the second half, and was immediately substituted at the Estadio San Juan del Bicentenario.
Messi grimaced as he left the field to be replaced by Ever Banega to leave a serious question mark over whether he will be fit to lead Argentina’s challenge in the Copa America, which gets under way next week in the United States.
The five-time Ballon d’Or winner found the net once and provided three assists in his country’s march to the final of the competition last year and as their second highest goalscorer of all-time, the Albiceleste will hope he recovers in time for their opener against defending champions Chile on 6 June.
The Barcelona forward was unsurprisingly the focal point of Argentina’s attacks early on and the home side deservedly took the lead just after the half hour through a bit of brilliance from Gonzalo Higuain.
The Napoli striker collected the ball from Marcos Rojo, twisted into the area before nutmegging a Honduran defender and chipping over goalkeeper Donis Escober.
Messi was withdrawn in the 64th minute although Argentina continued to press forward, with Escober producing a fine save from substitute Sergio Aguero while Gabriel Mercado hit the woodwork with his effort.
Banega could have killed the game off as the game entered its closing stages and although his dipping strike was denied by Escober, Argentina claimed a confidence-boosting win, albeit one that did not come without its pitfalls.