The efficacy of bacille Calmette–Guerin (BCG) vaccination against tuberculosis is highly variable, and protective immunity elicited by BCG is poorly understood. We compared the cytokine/chemokine profiles of peripheral blood mononuclear cells (PBMC) obtained from infants BCG-vaccinated at birth to those of PBMC obtained from infants before (delayed) BCG vaccination. The PBMC from 10-week-old BCG-vaccinated infants released higher levels of pro-inflammatory molecules than PBMCs from the nonvaccinated counterpart. In vitro exposure of PBMCs from BCG-vaccinated infants, but not nonvaccinated infants, to two different Mycobacterium tuberculosis strains showed distinct pro- and anti-inflammatory cytokine/chemokine patterns. Thus, BCG-induced infant immune responses and their potential protective capacity may be shaped by the nature of the infecting Mtb strain.