Despite another marathon negotiating session that dragged from Tuesday morning until Wednesday night — with only a brief respite for sleep — Major League Baseball and the players’ union could not reach a labor deal ahead of yet another self-imposed deadline by the league. As a result, M.L.B. Commissioner Rob Manfred announced on Wednesday night that another week of regular season games has been canceled.

“Because of the logistical realities of the calendar, another two series are being removed from the schedule, meaning that Opening Day is postponed until April 14th,” Manfred said in a statement. “We worked hard to reach an agreement and offered a fair deal with significant improvements for the players and our fans. I am saddened by this situation’s continued impact on our game and all those who are a part of it, especially our loyal fans.”

Although M.L.B. had once threatened not to reschedule canceled games — nor pay players for them — the league offered the union a chance this week to play a full 162-game season with rescheduled games, and thus full pay and service time.

The sides spent all day Tuesday negotiating, and the conversations carried over into the wee hours of Wednesday. The union asked for — and received — time to confer with its executive board of players in the morning regarding the league’s latest offer and then to return with its counterproposal. In the early afternoon, union officials departed M.L.B.’s offices in Manhattan after presenting their response and returned to their own headquarters a few blocks away.

There was progress in recent days, and the proposals advanced significantly. But it wasn’t enough to strike a deal or end the lockout — already the second-longest work stoppage in the league’s history.

On March 1, when the sides failed to agree to a new pact ahead of the first self-imposed deadline from the league, Manfred called off the first two series of the regular season, which had been scheduled to begin on March 31. More than 75 games through April 6 were lost.

Early last month, Manfred said losing regular-season games would be “disastrous” for the industry. M.L.B. has now canceled games twice since Manfred enacted the lockout on Dec. 2.

Sensing the urgency this week, the sides began making progress on big issues — such as the luxury tax system or a bonus pool for players not yet eligible for salary arbitration — on Monday and into Tuesday. The packages of proposals evolved repeatedly, but the implementation of an international draft and the elimination of the qualifying-offer system emerged as big hurdles on Wednesday.

Now an already tense and complicated labor dispute could get even thornier over a significant issue: pay and service time for players tied to the missed games.

Though M.L.B. changed its stance this week on canceled games, the wiggle room in the calendar is getting smaller. With further delays, it is unlikely that there will be enough time to reschedule two weeks’ worth of games while keeping the same dates for the World Series in October.

In M.L.B.’s eyes, lost games mean less revenue for its clubs, and thus the league does not believe it should have to compensate players for those missed contests. The union’s position has been that the players will demand full pay and service time for games that M.L.B. unilaterally canceled, or they will attempt to have them rescheduled.

The previous two collective bargaining agreements had been viewed as further tilting the balance of power and economics in the owners’ favor. Realizing that significant changes to the system would be tense and full of brinkmanship, the union spent years preparing for this very fight against M.L.B. owners, who ran an $11 billion-a-year business before the coronavirus pandemic.

With the latest developments, the sides face the high likelihood of the first games being missed because of a work stoppage since the 1994-95 players’ strike, which resulted in the cancellation of more than 900 games and the 1994 World Series. That remains the longest work stoppage in baseball history.