To determine whether developmental nicotine exposure (DNE) alters the ventilatory and metabolic response to hyperthermia in neonatal rats (postnatal age 2–4 days), pregnant dams were exposed to nicotine (6 mg kg−1 of nicotine tartrate daily) or saline with an osmotic mini-pump implanted subdermally on day 5 of gestation. Rat pups (a total of 72 controls and 72 DNE pups) were studied under thermoneutral conditions (chamber temperature 33°C) and during moderate thermal stress (37.5°C). In all pups, core temperature was similar to chamber temperature, with no treatment effects. The rates of pulmonary ventilation (JOURNAL/jphy/04.02/00005245-201512010-00017/ENTITY_OV0312/v/2017-10-03T051218Z/r/image-pngI), O2 consumption (JOURNAL/jphy/04.02/00005245-201512010-00017/ENTITY_OV0312/v/2017-10-03T051218Z/r/image-pngO2) and CO2 production (JOURNAL/jphy/04.02/00005245-201512010-00017/ENTITY_OV0312/v/2017-10-03T051218Z/r/image-pngCO2) did not change with hyperthermia in either control or DNE pups. However, JOURNAL/jphy/04.02/00005245-201512010-00017/ENTITY_OV0312/v/2017-10-03T051218Z/r/image-pngI was lower in DNE pups at both chamber temperatures, whereas the duration of spontaneous apnoeas was longer in DNE pups than in controls at 33°C. The JOURNAL/jphy/04.02/00005245-201512010-00017/ENTITY_OV0312/v/2017-10-03T051218Z/r/image-pngI/JOURNAL/jphy/04.02/00005245-201512010-00017/ENTITY_OV0312/v/2017-10-03T051218Z/r/image-pngO2ratio increased at 37.5°C in control pups, although it did not change in DNE pups. To simulate severe thermal stress, additional pups were studied at 33°C and 43°C. JOURNAL/jphy/04.02/00005245-201512010-00017/ENTITY_OV0312/v/2017-10-03T051218Z/r/image-pngI increased with heating in control pups but not in DNE pups. As heat stress continued, gasping was evoked in both groups, with no effect of DNE on the gasping pattern. Over a 20 min recovery period at 33°C, JOURNAL/jphy/04.02/00005245-201512010-00017/ENTITY_OV0312/v/2017-10-03T051218Z/r/image-pngI returned to baseline in control pups but remained depressed in DNE pups. In addition to altering baseline JOURNAL/jphy/04.02/00005245-201512010-00017/ENTITY_OV0312/v/2017-10-03T051218Z/r/image-pngI and apnoea duration, DNE is associated with subtle but significant alterations in the ventilatory response to hyperthermia in neonatal rats.