By Azania Post Reporter
Mc Cain , who is battling brain cancer, said he "cannot in good conscience" vote for the new plan, which President Donald Trump backs.
The senator said it was wrong to pass such far-reaching legislation without input from the Democrats.
It is the second time he has thwarted his party leadership on the issue.
President Trump, speaking in Alabama late on Friday, condemned Republicans who did not back the new legislation, saying: "They don't have the guts to vote for it."
Republicans need 50 votes in a 100-seat chamber they control 52-48 to succeed.
With Democrats united in opposition, there is little margin for error.
McCain's objection could doom conservatives' seven-year campaign to erase Democratic former President Barack Obama's signature legislative achievement.
The Arizona senator said such a bill demands extensive hearings, debate and amendment.
"That is the only way we might achieve bipartisan consensus on lasting reform," he wrote, "without which a policy that affects one-fifth of our economy and every single American family will be subject to reversal with every change of administration and congressional majority."
McCain said he could not support a rushed bill "without knowing how much it will cost, how it will effect sick insurance premiums, and how many people will be helped or hurt by it".
One other Republican senator, Rand Paul, is also against the party's latest bill.
At least four other Republican senators are undecided: Lisa Murkowski, Dan Sullivan, Rob Portman and Jerry Moran.
Experts say as several Republican senators explained - ones who were firm "yesses" - the main attraction for the plan was that it was the only plan on the table.
Now it appears Republicans will have to go back to the drawing board.
Although the end of September is the deadline for passing a bill with a simple majority in the Senate for this federal budget, there's no reason the party couldn't start the wheels turning for another vote next year - or, conceivably, simply change the rules, as Donald Trump has suggested.
None of that will alter the simple dynamic that made itself clear over the course of the past months, however.
The Republican Party, despite campaigning ferociously for Obamacare repeal for nearly seven years, could never agree on how to turn those promises into reality without sending the healthcare industry into a tailspin.