The twice-yearly mass distribution of azithromycin to children aged 1-59 months reduces all-cause child mortality. It has been suggested in some studies that mass azithromycin distributions may reduce malaria mortality and parasitemia; however, these studies have been conducted in the absence of seasonal malaria chemoprevention (SMC). Here, we evaluate malaria parasitemia in a cluster randomized trial of azithromycin versus a placebo in Burkina Faso, where SMC was being administered. Thin and thick smears were taken from a random sample of 15 children per cluster in 40 clusters that had been receiving twice-yearly azithromycin or a placebo for 36 months (six distributions). We found no evidence of a difference in malaria parasitemia between children in the azithromycin and placebo clusters (mean difference -6% prevalence; 95% CI -17% to 6%; P = 0.33). These results suggest that reductions in malaria parasitemia may not be a major contributor to the effect of azithromycin on child mortality in settings in which SMC is administered.