The warning said 45 mph wind and higher gusts could be expected Monday afternoon and evening on the Avalon Peninsula.
A tropical storm watch was issued for the Burin Peninsula and Bonavista Peninsula. Warnings mean tropical storm conditions, with sustained wind of at least 39 mph, are expected; watches mean they are possible.
At 11 a.m. EDT, Isaac had top sustained wind near 60 mph, down from 75 mph, just over hurricane strength, earlier in the day, the National Hurricane Center said.
The storm was centered about 190 miles south-southwest of Newfoundland's Cape Race, or some 800 miles east of Portland, Maine, and was moving north-northeast at about 41 mph. Its center was expected to pass over or near southeastern Newfoundland later Monday.
Isaac's wind and rain were likely to be comparable to a typical winter storm, said Chris Landsea, a meteorologist at the hurricane center in Miami. Forecasters said the storm was expected to continue weakening and begin losing its tropical characteristics.
Newfoundland was hit by 100 mph wind gusts from the remnants of Hurricane Florence on Sept. 14.
Isaac was the fifth hurricane and ninth named storm of the Atlantic hurricane season, which began June 1 and ends Nov. 30.