"Clearly this is a bump in the road, but I don't think it changes the overall landscape," Cornyn told reporters, adding that he expects Republicans to win in both states in November.
But the GOP's path now relies on the party's ability to win states Obama is targeting. Republican strategist Dan Judy said that puts the onus on the eventual Republican presidential nominee to win while carrying swing states such as Virginia, Wisconsin, Florida, New Mexico and Ohio — all of which Democrats are defending in the Senate.
"I think a majority is still possible, but the road to 51 is much tougher today, and much more dependent on a strong showing by the presidential nominee at the top of the ticket," Judy said. "But if Obama wins re-election, it's much more unlikely — although not impossible — that the Republicans will be able to win enough of those to take the Senate."
Democratic Senatorial Campaign Committee Chairwoman Patty Murray (Wash.) said on MSNBC's "Andrea Mitchell Reports" that she was "very excited" about Kerrey's candidacy and called the open seat in Maine "a great opportunity."
The GOP candidate field in Nebraska is set, and a viable nominee should emerge from the May 15 primary between Attorney General Jon Bruning, state Treasurer Don Stenberg and state Sen. Deb Fischer. That leaves five months for the nominee to run a competitive campaign in a strongly Republican state.
But Snowe's retirement caught Republicans off guard, and Cornyn conceded that the NRSC is still assessing the political environment in Maine and the potential list of GOP candidates. With a March 15 filing deadline, Republicans don't have much time to recruit a strong successor to Snowe, if one exists. Democratic Reps. Chellie Pingree and Mike Michaud have already taken steps toward running.
Sen. Jim DeMint (R-S.C.) and other Republicans were not immediately as buoyant about their prospects of holding the seat as Cornyn was, with a few acknowledging that it would make it harder for the GOP to win the Senate majority.
"I think it is a blow," DeMint said.
The South Carolinian, who is active in endorsing and financially supporting candidates through his Senate Conservatives Fund political action committee, said he would also examine whether to get involved in Maine's June 12 GOP primary. He noted that time was short and said he had not previously paid attention to Maine because he expected Snowe would run for re-election and easily hold the seat.
In 2010, Republicans captured the governor's mansion in Maine and took control of both chambers of the state Legislature.
Snowe and Sen. Susan Collins (R) have represented the state for years, even as it grew more liberal with the rest of New England. Collins, during a brief interview Wednesday, agreed with Cornyn's optimism, contending that while the seat is no longer the "sure bet" that it was for the GOP, it is still very winnable.
Senate Republican Conference Chairman John Thune (S.D.) argued that flipping the chamber was already a "heavy lift" before Snowe's retirement.
"Obviously, we don't know exactly what the candidates may be yet," Thune said. "But we're hoping that we'll have a good one."