If the first day was any indication, the race to replace retiring Sen. Barbara A. Mikulski (D-Md.) could be a free-for-all.

Senate seats are highly coveted by politicians, because once won, they’re rarely lost. The 2016 contest to replace Mikulski will be only the second since she became a senator three decades ago that does not have an incumbent on the ballot.

So by Monday afternoon, just hours after Mikulski’s surprise announcement that she would step down at the end of her fifth term, no fewer than six of Maryland’s seven House members had signaled that they might take a shot at replacing her. An aide to one of them, Rep. Chris Van Hollen (D), said he is “very likely” to run.

Former governor Martin O’Malley (D) remained mum, but there was speculation he could shift his ambitions from a long-shot presidential bid to a race that would be more easily winnable. Associates of former lieutenant governor Anthony G. Brown (D), who lost last year’s governor’s race, put out the word that he is “seriously considering” a Senate bid.

And no fewer than a half-dozen other names, including Baltimore Mayor Stephanie Rawlings-Blake (D), were being floated — and that’s just on the Democratic side. Buoyed by a GOP victory in last year’s governor’s race, Republicans were already talking about multiple candidates, including former governor Robert L. Ehrlich Jr. and Rep. Andy Harris.

“Almost anyone who has made their mark in Maryland politics is going to look at this race,” said Mike Morrill, a longtime Democratic strategist in Maryland. “An opportunity like this just doesn’t come along very often.”

That means Democrats are facing a big, potentially bruising — and very expensive — primary while they’re still licking their wounds over Brown’s loss to Republican Larry Hogan in the governor’s race.

The Senate race is likely to draw several candidates from the voter-rich Washington suburbs, which could accelerate a shift in power toward a region that has not produced a successful candidate for governor or U.S. Senate since the 1990s.

Both Mikulski and her Senate colleague, Benjamin L. Cardin, are from the Baltimore area, as was Cardin’s long-serving predecessor, Paul S. Sarbanes.

The Senate contest could have implications well down the ballot, too, as candidates could give up the seats they hold to take a shot at higher office. That could mean opportunities for younger or aspiring officeholders who have felt stymied by longer-serving politicians.

“It creates turmoil down the entire chain,” Maryland Senate President Thomas V. Mike Miller Jr. (D-Calvert) told the Baltimore Sun, predicting a wide-open primary season. “There is no party boss. There is no party discipline.”

Some Democrats said the Senate seat could be tempting for O’Malley, who has yet to get much traction for a presidential bid in which he would likely face Hillary Rodham Clinton.

Sen. Barbara Mikulski (D-Md.), who announced her retirement on Monday, is the longest-serving woman in Congress.

But Steve Kearney, a former O’Malley aide who has helped raise money for his political action committee, was among several people close to the former governor who said he is more likely to stay on his present course. “He’d be a good candidate, but he’s more of an executive,” Kearney said. “That’s always been his strength.”

Still, said Morrill, a Senate race is “something he’s got to consider. It’s a seat that he has a good chance of winning.”

O’Malley spokeswoman Lis Smith declined to comment. “Today is a day to reflect on Senator Mikulski’s service to the people of Maryland,” she said.

O’Malley and Mikulski have been close for decades, and his mother works as Mikulski’s receptionist. Mikulski has been cool to the idea of an O’Malley presidential bid, however, announcing she will support Clinton if the former secretary of state runs.

Mikulski, the longest-serving woman in Congress, has a history of supporting women for the Senate, which could affect a potential endorsement. The only woman in Maryland’s House delegation — Rep. Donna F. Edwards (D) of Prince George’s County — was among those being talked about as a possible successor.

Rep. John Delaney (D), a wealthy former investment banker who narrowly won reelection last year, was the most public about his intentions, commenting on Twitter that he plans to explore a bid. “I’m in public service to get things done,” he tweeted.

A spokeswoman for Rep. C.A. Dutch Ruppersberger (D), whose district is rooted in Baltimore County, said “it’s safe to say” he will consider running for Mikulski’s seat.

Three other Democrats in Maryland’s House delegation were also being touted Monday as potential Senate candidates: Van Hollen and Reps. Elijah E. Cummings and John Sarbanes, the son of the former senator.

Van Hollen, a former aide on the Senate Foreign Relations Committee who lives in Montgomery County, in particular has been touted in the past as a possible Mikulski successor. In the past six years, however, he has become an increasingly loyal understudy to House Minority Leader Nancy Pelosi (D-Calif.), who has at times considered retiring.

Other names being talked about on the Democratic side include U.S. Labor Secretary Thomas Perez, a former Montgomery County Council member and state-level Cabinet secretary, and former Montgomery County delegate Heather Mizeur, a progressive who outperformed expectations in the last Democratic gubernatorial primary.

In addition to Ehrlich and Harris, names being floated on the Republican side include former Republican National Committee chairman Michael S. Steele, who was lieutenant governor under Ehrlich, and Dan Bongino, who challenged Delaney last year and was the Republican Senate nominee in 2012.

Harris’s office issued a statement Monday praising Mikulski’s lengthy service and saying he is considering the race.

Paul Kane and Jenna Johnson contributed to this report.