The study by the Fred Hutchinson Cancer Research Center also found that maintaining the same weight over time appears to have a positive effect on a woman's immune system, according to one of the lead researchers.
Researchers in the study, published Tuesday in the Journal of the American Dietetic Association, interviewed 114 overweight but otherwise healthy sedentary, older women about their weight-loss history during the past 20 years. The women had to have maintained a stable weight for at least three months before joining the study, which was funded by the National Cancer Institute.
The study, which found that long-term immune function decreases in proportion to how many times a woman has intentionally lost weight, measured natural killer cell activity in the women's blood. Natural killer cells are an essential part of the immune system, killing viruses and leukemia cells, said Cornelia Ulrich, senior author and an assistant member of the Hutchinson Center's Public Health Sciences Division.
Low natural killer cell activity has been associated with increased cancer rates and "just a higher susceptibility toward any type of infection," she told CBS News Correspondent Barry Bagnato.
"While one weight-loss episode of 10 pounds or more in the previous 20 years was not associated with current natural killer cell activity, more frequent weight-loss episodes" were associated with a significant decrease in such activity, Ulrich said.
"Immune function was higher among women who had been fairly weight-stable," Ulrich said.
Those who reported losing weight more than five times had about a third lower natural killer cell function, the study found. Conversely, women who maintained the same weight for at least five years had 40 percent greater natural killer cell activity as compared to those who maintained their weight for fewer than two years.
Though no men participated in the study and further research is needed, Ulrich said the immune systems of male dieters would likely be affected the same way.
"It's really the first study to show potential long term effects of yo-yo-dieting on immune function," she said.
The findings, while intriguing, are preliminary, cautioned Ulrich, who is also a research assistant professor in epidemiology at the University of Washington School of Public Health and Community Medicine.
Researchers had to rely on the participants' own reports of their weight loss histories and the analysis was based on blood samples collected at a single point in time, representing a narrow sample.
A long-term study could provide more conclusive results, said Ulrich, who is planning to collaborate with Canadian researchers who have been working on a similar study.
Although the study suggests that yo-yo dieting is harmful, Ulrich stopped short of saying that people should stop attempting to lose weight.
"There's clearly evidence that weight loss is beneficial for your health," she said. "What we're concerned about is this pattern of weight cycling where women go up and down."
Exercise has been shown to boost immunity and temper some of the negative effects of weight loss on the immune system, Ulrich said.
Despite its preliminary nature, the study is significant, said Katherine Tallmadge, a spokeswoman for the American Dietetic Association in Washington, D.C. Although dietitians have known for years the negative psychological effects of yo-yo dieting, this appears to be the first study to examine the long-term impact of such dieting on immunity, she said.
People should avoid popular low-carb and low-fat diets that can produce initial weight loss but rarely work in the long term, Tallmadge said.
"Study after study shows that more moderate restrictions are more likely to last permanently," Tallmadge said. "That's why we registered dietitians are urging people not to do the fad diets, and just try small changes that they're more likely to be able to live with — even if the weight loss is slower."