Speaking at a local Chamber of Commerce event in Middletown, Kentucky on Thursday, McConnell, in video posted by a local news outlet CN/2, didn't specifically link the party's diminishing standing to GOP presidential candidate Donald Trump's slide in both national polls and those in key battleground states.
But the GOP leader said the challenging landscape for Republicans in 2016 was because they are defending more seats than the Democrats.
"It's very dicey," McConnell said. "We have, we -- meaning Senate Republicans -- have 24 members up. Our Democratic friends only have 10. So as you can see we were going to be on defense anyway, no matter what was going on at the presidential level."
He added, "I may or may not be calling the shots next year. If I'm not, it'll be a guy called Chuck Schumer from New York (as Senate majority leader) who has a very different mindset from myself, and our ability to impact judicial appointments will be considerably diminished if those guys are in the majority as opposed to us."
Republican hold 54 seats now; Democrats would need to pick up four seats to take control if Clinton wins the White House and five if Trump wins, because of the vice president's tie-breaking vote in the chamber.
McConnell, who has publicly backed Trump, didn't hold back about his assessment of the billionaire candidate's current political position, saying about both Trump and Hillary Clinton, "It is a statement of the obvious that neither of these nominees are widely appealing to the American people -- to put it mildly."
Referring to his interaction with Clinton during her time in the Senate, McConnell said she is "certainly smart and capable, but there are a lot of problems with Hillary Clinton."
He said Clinton's email scandal wouldn't top his list of issues, but pointed to issues with the Clinton Foundation during her tenure as Secretary of State as "a major sort of ethical blind spot. She ought not be President of the United States."
Without mentioning his own party's nominee, McConnell said he's advising GOP candidates to stay focused on those issues.
Earlier on Thursday, Senate Minority Leader Harry Reid held a conference call with reporters to try to link McConnell and vulnerable GOP Senators to Trump, arguing their position of blocking a vote on President Barack Obama's nominee to the Supreme Court Merrick Garland, meant they were Trump's "minions."
"As long as they're holding a Supreme Court seat open for him they are his minions, they are his enablers. This is the legacy of Mitch McConnell and the Senate Republicans, who stand behind Trump in refusing their constitutional duties for a bigot who is clearly unfit for office," Reid said.