We examined levels of the damage-associated molecular pattern molecules, HMGB1 and S100A9, in individuals for whom stored samples were available before and after antiretroviral therapy (ART) initiation, to determine their association with CD4 reconstitution. Mean HMGB1 levels (1.95 ng/ml vs. 3.02 ng/ml) and the proportion of individuals with detectable S100A9 (19.6% vs. 43.1%) significantly increased after ART. Detectable post-ART S100A9 was independently associated with impaired immune reconstitution.