The role of serotonin (5-HT) neurons in cardiovascular responses to acute intermittent hypoxia (AIH) has not been studied in the neonatal period. We hypothesized that a partial loss of 5-HT neurons would reduce arterial blood pressure (BP) at rest, increase the fall in BP during hypoxia, and reduce the long term facilitation of breathing (vLTF) and BP following AIH. We exposed 2 week-old, 5,7-dihydroxytryptamine (5,7-DHT)-treated and controls to AIH (10% O₂; n=13 control, 14 treated), acute intermittent hypercapnia (AIHC; 5% CO₂; n=12 and 11), or acute intermittent hypercapnic hypoxia (AIHH; 10% O₂, 5% CO₂; n=15 and 17). We gave five 5-min challenges of AIH and AIHC, and twenty ~20 sec challenges of AIHH to mimic sleep apnea. Systolic (sBP), diastolic (dBP), mean arterial pressure (MAP),heart rate(HR),and metabolic rate (VO₂) were continuously monitored. 5,7-DHT induced an ~35% loss of 5-HT neurons from the medullary raphe. Compared to controls, pups deficient in 5-HT neurons had reduced resting sBP (~6 mmHg), MAP (~5mmHg), HR (56 beats/min),and experienced a reduced drop in BP during hypoxia. AIHH induced vLTF in both groups, reflected in increased VE and VE/VO₂,and decreased arterial PaCO₂. The sBP of pups deficient in 5-HT neurons, but not controls, was increased 1 hr following AIHH. Our data suggest that a relatively small loss of 5-HT neurons compromises resting BP and HR, but has no influence on ventilatory plasticity induced by AIHH. AIHH may be useful for reversing cardio-respiratory defects related to partial 5-HT system dysfunction.