Variation in energy expended by preterm infants may be due to infant maturity and history of resolved acute lung disease (respiratory distress syndrome [RDS]) as well as growth, caloric intake, and activity. Indirect calorimetry was used in this exploratory, short-term longitudinal study to estimate energy expenditure (EE) from measures of inspired and expired O2 and CO2. The sample included 35 assessments for 10 preterm infants (5 with and 5 without RDS history). Lung disease history (resolved RDS, no RDS diagnosis), weight gain (g/d) from the day on which birth weight had been regained to the study day, mean activity level, the number of the assessment (1-6), and the interaction of lung disease history and time were included in a linear mixed model for repeated measures. Time was an index of postconceptional and postnatal age; all 3 were highly correlated. Because of high correlation with weight gain, caloric intake was not included in the analytic model. Lung disease history, mean activity level, and time were significant contributors to EE. A more precise measure of medical status than absence or presence of lung disease history, evenly spaced repetitions of EE assessment, and exploration of contexts in which the infants exhibit a higher activity level are needed in a replication study with a larger sample.