Abstract Purpose We hypothesised that during a rest-to-exercise transient in hypoxia (H), compared to normoxia (N), (i) the initial baroreflex sensitivity (BRS) decrease would be slower and (ii) the fast heart rate (HR) and cardiac output (CO) response would have smaller amplitude (A₁) due to lower vagal activity in H than N. Methods Ten participants performed three rest-to-50 W exercise transients on a cycle-ergometer in N (ambient air) and three in H (inspired fraction of O₂ = 0.11). R-to-R interval (RRi, by electrocardiography) and blood pressure profile (by photo-plethysmography) were recorded non-invasively. Analysis of the latter provided mean arterial pressure (MAP) and stroke volume (SV). CO = HR·SV. BRS was calculated by modified sequence method. Results Upon exercise onset in N, MAP fell to a minimum (MAPmin) then recovered. BRS decreased immediately from 14.7 ± 3.6 at rest to 7.0 ± 3.0 ms mmHg⁻¹ at 50 W (p < 0.01). The first BRS sequence detected at 50 W was 8.9 ± 4.8 ms mmHg⁻¹ (p < 0.05 vs. rest). In H, MAP showed several oscillations until reaching a new steady state. BRS decreased rapidly from 10.6 ± 2.8 at rest to 2.9 ± 1.5 ms mmHg⁻¹ at 50 W (p < 0.01), as the first BRS sequence at 50 W was 5.8 ± 2.6 ms mmHg⁻¹ (p < 0.01 vs. rest). CO-A₁ was 2.96 ± 1.51 and 2.31 ± 0.94 l min⁻¹ in N and H, respectively (p = 0.06). HR-A₁ was 7.7 ± 4.6 and 7.1 ± 5.9 min⁻¹ in N and H, respectively (p = 0.81). Conclusion The immediate BRS decrease in H, coupled with similar rapid HR and CO responses, is compatible with a withdrawal of residual vagal activity in H associated with increased sympathetic drive.