At least 177 people died from West Nile in 2006 out of 4,269 reported cases, the CDC said. The number of deaths was the greatest since 2003, when 264 people died out of nearly 10,000 cases.
The deadliest year for West Nile was 2002, when 284 people died.
In 2006, the nation also saw a 14 percent increase in the most serious West Nile cases involving encephalitis, meningitis or paralysis, according to the CDC's Morbidity and Mortality Weekly Report.
Those severe cases are the most likely to be reported to health authorities and are considered the most reliable measurement of the illness's impact on the U.S. population from year to year.
Some experts blamed the West Nile spike on weather, saying last summer's heat wave may have contributed to mosquito breeding and activity. It was comparatively cool in 2004 and 2005.
The worst of the 2006 season occurred out West, with nearly 1,000 cases in Idaho alone. Human cases along the Eastern seaboard have been declining since West Nile first appeared in the United States, in New York, in 1999.
Some health officials worry that cuts in federal funding could lead to more illness.
CDC funding for West Nile prevention dropped from $45 million last year to $27 million this year, although an added $8 million was set aside for Louisiana in the wake of Hurricane Katrina.
As a result, states are cutting back testing of dead birds and mosquitoes. Some are also considering reductions in human testing.
"I am concerned," said Karen Yates of the Missouri Department of Health and Senior Services. She said testing of dead birds provided an "early warning system" for much of the state. "I wish we hadn't lost that capacity."