To investigate the association between African ancestry and neutrophil counts among children living with HIV (CLWH). We also examined whether medications, clinical conditions, hospitalization, or HIV virologic control were associated with low neutrophil counts or African ancestry. We conducted a secondary analysis of the Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) Study, a multicenter prospective cohort study of CLWH across 8 Canadian pediatric HIV care centers. We classified CLWH according to African ancestry, defined as "African," "Caribbean," or "Black" maternal race. Longitudinal laboratory data (white blood cells, neutrophils, lymphocytes, viral load, and CD4 count) and clinical data (hospitalizations, AIDS-defining conditions, and treatments) were abstracted from medical records. Among 217 CLWH (median age 14, 55% female), 145 were of African ancestry and 72 were of non-African ancestry. African ancestry was associated with lower neutrophil counts, white blood cell counts, and neutrophil-lymphocyte ratios. Neutrophil count <1.5 × 109/L was detected in 60% of CLWH of African ancestry, compared with 31% of CLWH of non-African ancestry (P < 0.0001), representing a 2.0-fold higher relative frequency (95% CI: 1.4-2.9). Neutrophil count was on average 0.74 × 109/L (95% CI: 0.45 to 1.0) lower in CLWH of African ancestry (P < 0.0001). Neither neutrophil count<1.5 × 109/L nor African ancestry was associated with medications, hospitalizations, AIDS-defining conditions, or markers of virologic control (viral load, sustained viral suppression, and lifetime nadir CD4). In CLWH, African ancestry is associated with lower neutrophil counts, without clinical consequences. A flexible evaluation of neutrophil counts in CLWH of African ancestry may avoid unnecessary interventions.