INTRODUCTION: It is known that respiratory muscles are prone to fatigue in women with systemic lupus erythematosus (SLE) but the extent to which this limits their cardiorespiratory capacity is yet unclear. PURPOSE: This study characterized the ventilatory response during maximal exercise testing in women with SLE, examining the potential contribution of respiratory muscle fatigue to diminished cardiorespiratory fitness. METHODS: Fifteen women participated in the study (control: n=7, age= 36±8 yr, SLE: n=8, age=37±9 yr). Each subject performed a modified Bruce treadmill exercise test to volitional exhaustion. The ventilatory response was characterized by measures of expired minute volume (Ve), tidal volume (Vt), respiratory rate, expiratory time (Te), ventilatory quotients for O2 and CO2 and ventilation-perfusion matching using expired gas analysis and exponential rise CO2 rebreathing methods. RESULTS: Women with SLE had lower Vt (1449±83 vs 1795±124 ml; p=0.04) and Ve (61±6.7 vs 71.4±4.1, Cohen’s ES=0.70) and prolonged Te (42±2.5 vs 32±2.3 ms, p=0.03) compared to the control group. Significant differences of the other cardiorespiratory measures were not observed. The time to exhaustion during the exercise test (13±0.70 vs 17±0.46 min ; p=0.02) and peak VO2 (21±1 vs 29± 2 ml/kg/min p= 0.01) were significantly diminished in those with SLE. CONCLUSION: Poor cardiorespiratory endurance has been reported in women with SLE. In the current study, group similarity in ventilatory efficiency and ventilation-perfusion matching eliminate the observation of any impairment of ventilatory drive. Conversely, the decline in Ve and Vt, and an increase in Te, coupled with a decreased time to exhaustion suggest that respiratory muscle fatigue may have contributed to low cardiorespiratory fitness and endurance in these subjects. NIH/NICHD 1R03HD39775