Matthews had wrist surgery Aug. 13 and the Maple Leafs announced at the time his recovery would take a minimum of six weeks.
The 24-year-old center led the NHL in goals last season with 41 in 52 games; he missed four games with a wrist injury. He has been participating in the majority of team drills since joining the main group at training camp Sept. 28.
"I just don't feel I'm where I want to be as far as my wrist goes right now," Matthews said after practice Monday. "We're taking it day by day and lots can change, but as of right now this week is probably out of the question. But you never know what could happen."
The Maple Leafs open the regular season at home against the Montreal Canadiens on Wednesday (7 p.m. ET; SN, TVAS, ESPN+, NHL LIVE), then play at the Ottawa Senators on Thursday and the Senators at home Saturday.
Matthews could return for their fourth game, against the New York Rangers at home Oct. 18.
"I'm not expecting him to be available for the first three games," Toronto coach Sheldon Keefe said. "Auston is not at the point right now where he is feeling comfortable playing. He is still not quite there so he is not going to be available for us this week, which is why you saw him in a different jersey and not part of a line today."
John Tavares played center in Matthews' usual spot between left wing Nick Ritchie and right wing Mitchell Marner.
Alex Kerfoot was the center on the second line with Michael Bunting and William Nylander.
Bunting moved up to replace Ilya Mikheyev, who injured his thumb in the Maple Leafs' final preseason game Saturday. The injury will require surgery and Mikheyev is expected to be out eight weeks.
"I hadn't put John [with Ritchie and Marner] save for a few shifts through camp because we were counting on the fact that Auston was gearing toward being available," Keefe said. "But I like John in that spot. We've used Kerfoot with Nylander and Mikheyev throughout a lot of camp, but now without Mikheyev we put Bunting there and we are confident with that."
Matthews said he did not have a setback in his recovery and he's been pleased with his progression while working toward returning.
"The progress has been great," he said. "Physically I feel great out there. I feel like in the last month or so I've been able to get in some really good work with the skills coaches, working on different parts of my game. I just don't personally feel like I'm at the point where I'm 100 percent comfortable to play, that's really all it is. I feel good physically and everything, I think I need a little bit more time."
Matthews said he understands that being patient makes the most sense, as difficult as it will be not to be in the lineup Wednesday.
"I'm dying to get in and play honestly, and get reps in with the guys," he said. "But it's just one of those things where I have to be patient with it and be disciplined and make sure I'm 100 percent comfortable going in."
Keefe said the goal is to have Matthews play without the discomfort he felt last season.
"Our most important thing right now is to make sure he is 100 percent comfortable," he said. "He went through a season last season where he was not playing at 100 percent and he's gone through this procedure to be in that position, so we'll make sure we are patient enough to allow that to happen. He looks terrific on the ice and it shows the impact he is going to have when he gets back in the lineup. He being 100 percent confident and comfortable is the most important thing for us."
