"Sen. Gregg has assured me that if this were to happen, if it were to happen, it would not change the makeup of the Senate," McConnell said on "Face the Nation" on CBS. "In other words, whoever is appointed to replace him would caucus with Senate Republicans, so I think it would have no impact on the balance of power in the Senate."
Lynch's spokesman, Colin Manning, declined comment on any agreement, saying only "this situation is still between the White House and Sen. Gregg."
Gregg spokeswoman Laena Fallon had no comment on McConnell's statement.
Replacing Gregg with someone other than a Democrat willing to side with the party would deny Democrats the legislative dominance they seek in the Senate. Sixty votes are required to end debate in the 100-member chamber, but Democrats have just 56 seats, plus two independents who caucus with them.
In spite of being in the minority, Republicans can bottle up legislation through a filibuster as long as they retain at least 41 votes. The outcome of Minnesota's disputed Senate contest would decide the matter.
Officials say Obama is set to make Gregg his third Republican Cabinet official as early as Monday.
Many officials in New Hampshire and Washington now think a scenario is almost certain in which Lynch names a Republican or an independent as Gregg's successor. Democratic leaders have warned supporters in private that Gregg's departure would not automatically mean a Democratic replacement.
McConnell's second-in-command praised Obama's consideration of Gregg despite its potential political implications.
Sen. Jon Kyl, R-Ariz., cautioned that it's not a certainty that Lynch would appoint a fellow Democrat to replace Gregg. He also said he doubted that Republicans would lose the ability to filibuster if Gregg left, but he was less direct in discussing any potential deal among the White House, Gregg and Lynch.
"I'm not suggesting a deal at all," Kyl said. "I'm just suggesting that Sen. Gregg clearly has thought this through. And if it does turn out that he's the commerce secretary, that events may unfold in a way that don't cause us the problem that you suggested," he said on "Fox News Sunday."
Asked if Republicans might pressure Gregg to stay, Kyl said: "I'm not sure that we would. ... I suspect that Sen. Gregg has thought that through very carefully and would not leave his Republican colleagues in a lurch."
He added that Gregg "could make a significant contribution to the Obama administration."
Lynch, a political moderate who named Republican Kelly Ayotte as his attorney general, enjoys broad popularity and won re-election with 70 percent of the vote. Picking a Republican could help him build on his governing coalition.
Lynch is leaning toward naming a "placeholder" senator in the seat, someone who would not seek the job in two years. Former Reagan and George H.W. Bush administration official Bonnie Newman is leading the pack of potential replacements. She was a former top aide to Gregg, a Harvard dean and one of Lynch's first Republican supporters.
Others being discussed include former Republican state House Speaker Doug Scamman, a Lynch ally, and Democratic Rep. Paul Hodes, who was eyeing a Senate run in 2010 against Gregg.
Obama's Cabinet already has two Republicans: Defense Secretary Robert Gates, who was appointed by President George W. Bush and then asked by Obama to remain; and former Rep. Ray LaHood of Illinois, who did not seek re-election to the House in 2008 and soon after was named transportation secretary.
If Gregg were nominated, he would be Obama's second choice. A grand jury investigation over how state contracts were issued to political donors led New Mexico Gov. Bill Richardson to withdraw from consideration.