The estimate, released less than a week after Republicans in the upper chamber unveiled their health care legislation and just days ahead of a potential vote, could complicate the already hard task of getting enough GOP support to pass the measure.
"There's no way we should be voting on this next week", Republican Senator Ron Johnson warned on NBC's "Meet the Press" Sunday.
The White House responded by attacking the CBO, saying it has a "history of inaccuracy".
It is still unclear whether the new budget office projections will be judged against the House's version, or against the Affordable Care Act's coverage figures.
CBO represents the official analysis of the Senate's bill, though some Republicans have sought to cast doubt on its accuracy.
Paul said he would oppose a motion to proceed without assurances to improve the bill, and suggested there are other conservative senators who also will hold out.
Republicans can only afford to lose two members to pass the bill, which would then come down to a tie-breaking vote by Vice President Mike Pence. President Donald Trump has called the House version "mean" and called on Senate Republicans to approve legislation with more "heart". Dean Heller, R-Nev., who faces perhaps the toughest 2018 re-election race of any Senate Republican and has said he can't support the measure if huge numbers of people lose coverage. The CBO says this bill will knock 15 million people off their insurance next year.
That is pretty much all anybody needs to know about the Republican Party's push to repeal Obamacare-every piece of legislation the party produces amounts to a wealth transfer from the vulnerable to the rich that lowers premiums, though just slightly, for some younger and healthier Americans.
A person making $26,500 would pay more for coverage under the Senate law at ages 21, 40 and 64. This was supposedly an oversight, and earlier today McConnell announced a new provision that after a certain date would lock new health-insurance applicants out of the markets for six months, presumably encouraging them to enroll earlier.
The AMA said it was especially concerned with a proposal to put the Medicaid healthcare programme for the poor on a budget, saying this could "fail to take into account unanticipated costs of new medical innovations or the fiscal impact of public health epidemics, such as the crisis of opioid abuse now ravaging our nation".
The Senate bill would roll back much of Obama's health care overhaul.
For the first time, the Senate bill would cap federal spending on Medicaid in 2020, forcing state governments to either scale back the program or make up the difference out of their own budgets.
The big bad number most often cited in criticisms of the House-passed legislation did not get a lot better.
That's a decrease of over $770 billion on Medicaid over the next 10 years. The legislation also cuts Medicaid spending, reduces in federal assistance for Americans purchasing health care, and defunds Planned Parenthood, which is often the only source of affordable health care for low-income women, for a year. The largest increases in deficits would come from getting rid of Obamacare taxes that are not directly related to health insurance coverage. There are now around 29 million people without health insurance.
Moreover, the report blames actions of the Trump administration for driving some insurance companies out of the market, with "substantial uncertainty" over its enforcement of the requirement that individuals carry health insurance and its threats to withhold payment of cost-sharing subsidies.