Infants spend most of their indoor time at home; however, residential air quality is poorly understood. We investigated the air quality of infants’ homes in the New England area of the U.S. Participants (N = 53) were parents of infants (0–6 months) who completed telephone surveys to identify potential pollutant sources in their residence. Carbon monoxide (CO), carbon dioxide (CO2), particulate matter with aerodynamic diameter ≤0.5 µm (PM0.5), and total volatile organic compounds (TVOCs) were measured in 10 homes over 4–7 days, and levels were compared with health-based guidelines. Pollutant levels varied substantially across homes and within homes with overall levels for some homes up to 20 times higher than for other homes. Average levels were 0.85 ppm, 663.2 ppm, 18.7 µg/m3, and 1626 µg/m3 for CO, CO2, PM0.5, and TVOCs, respectively. CO2, TVOCs, and PM0.5 levels exceeded health-based indoor air quality guidelines. Survey results suggest that nursery renovations and related potential pollutant sources may be associated with differences in urbanicity, income, and presence of older children with respiratory ailments, which could potentially confound health studies. While there are no standards for indoor residential air quality, our findings suggest that additional research is needed to assess indoor pollution exposure for infants, which may be a vulnerable population.