Respiratory sinus arrhythmia (RSA) may be associated with improved efficiency of pulmonary gas exchange by matching ventilation to perfusion within each respiratory cycle. Respiration rate, tidal volume, minute ventilation (V˙e), exhaled carbon dioxide (V˙co ₂), oxygen consumption (V˙o ₂), and heart rate were measured in 10 healthy human volunteers during paced breathing to test the hypothesis that RSA contributes to pulmonary gas exchange efficiency. Cross-spectral analysis of heart rate and respiration was computed to calculate RSA and the coherence and phase between these variables. Pulmonary gas exchange efficiency was measured as the average ventilatory equivalent of CO₂(V˙e/V˙co ₂) and O₂(V˙e/V˙o ₂). Across subjects and paced breathing periods, RSA was significantly associated with CO₂ (partial r = −0.53,P = 0.002) and O₂ (partialr = −0.49, P = 0.005) exchange efficiency after controlling for the effects of age, respiration rate, tidal volume, and average heart rate. Phase between heart rate and respiration was significantly associated with CO₂ exchange efficiency (partial r = 0.40, P = 0.03). These results are consistent with previous studies and further support the theory that RSA may improve the efficiency of pulmonary gas exchange.