Argentina's all-time appearance holder and record goalscorer was forced to sit out March's two friendlies against El Salvador and Costa Rica.
However, he is now set to don the famous blue and white of Argentina for the first time since playing 78 minutes in November's 2026 World Cup qualifier with Brazil.
While Messi is poised to start, reports have suggested that Scaloni could give some fringe players the chance to impress as he continues to consider which three players should be cut from his 29-man provisional squad.
Lisandro Martinez may be given valuable game time after returning from injury to feature in Manchester United's final three matches of the campaign, including their 2-1 win over Manchester City in the FA Cup final.
The 26-year-old could line up alongside Cristian Romero, Gonzalo Montiel and Marcos Acuna, offering protection to Aston Villa shot-stopper Emiliano Martinez.
Scaloni could be keen to give minutes to Chelsea midfielder Enzo Fernandez, who is available after recovering from groin surgery.
Roma's Leandro Paredes may get a rare starting opportunity, having featured from the off in just one of Argentina's eight matches, and he could be joined in midfield by Tottenham Hotspur's Giovani Lo Celso.
Alejandro Garnacho is hoping to make his first appearance since scoring in Man United's FA Cup triumph at Wembley, with the youngster among those who could be considered to start in attack alongside Messi and one of Lautaro Martinez and Julian Alvarez.
The latter has tended to get the starting opportunities in recent times, but Martinez could be given the opportunity to start against Ecuador and stake a claim for the number nine spot ahead of this summer's Copa America in the USA.
Argentina possible starting lineup: E Martinez; Montiel, Romero, Li Martinez, Acuna; Paredes, Fernandez, Lo Celso; Messi, Garnacho, La Martinez