OBJECTIVE: A substantial number of children exposed to gestational opioids have neurodevelopmental, behavioral and cognitive problems. Opioids are not neuroteratogens but whether they affect the developing brain in more subtle ways (for example, volume loss) is unclear. We aimed to determine the feasibility of using magnetic resonance imaging (MRI) to assess volumetric changes in healthy opioid-exposed infants. STUDY DESIGN: Observational pilot cohort study conducted in two maternity hospitals in New South Wales, Australia. Maternal history and neonatal urine and meconium screens were obtained to confirm drug exposure. Volumetric analysis of MRI scans was performed with the ITK-snap program. RESULT: Scans for 16 infants (mean (s.d.) gestational age: 40.9 (1.5) weeks, birth weight: 3022.5 (476.6) g, head circumference (HC): 33.7 (1.5 cm)) were analyzed. Six (37.5%) infants had HC <25th percentile. Fourteen mothers used methadone, four used buprenorphine and 11 used more than one opioid (including heroin, seven). All scans were structurally normal whole brain volumes (357.4 (63.8)) and basal ganglia (14.5 (3.5)) ml were significantly smaller than population means (425.4 (4.8), 17.1 (4.4) ml, respectively) but lateral ventricular volumes (3.5 (1.8) ml) were larger than population values (2.1(1.5)) ml. CONCLUSION: Our pilot study suggests that brain volumes of opioid-exposed babies may be smaller than population means and that specific regions, for example, basal ganglia, that are involved in neurotransmission, may be particularly affected. Larger studies including correlation with neurodevelopmental outcomes are warranted to substantiate this finding.