To assess the effect of obesity on CD4 cell counts, we estimated the association of time-updated BMI categories with CD4 changes among 1001 documented HIV seroconverters. During the pre-highly active antiretroviral therapy (HAART) era, a higher BMI was associated with less reduction in CD4 cell counts over time. However during the HAART era, obese versus normal weight patients had smaller increases in CD4 cell counts (+69 versus +116 cells, P = 0.01). Lower CD4 cell counts may now be another adverse consequence of obesity.