Matthews, 22, reportedly tested positive for the coronavirus in May and subsequently went into quarantine at his home in Arizona.
The 6-foot-3 pivot racked up a career-best 47 goals and 80 points over 70 games during the shortened 2019-20 season, leading the club in both of those categories. Matthews was scoring at a 55-goal pace over 82 games, which would have set a single-season franchise record.
Teams will report to training camp Monday for Phase 3 of the NHL's return-to-play plan before traveling to their respective hub cities July 26. The qualifying round gets underway Aug.1. The Maple Leafs will meet the Columbus Blue Jackets in their best-of-five play-in series.