IntroductionSprint interval training (SIT), characterized by brief bouts of ‘supramaximal’ exercise interspersed with recovery periods, increases peak oxygen uptake (V˙O2peak$${\dot{\text{V}}}{\text{O}}_{2{\text{peak}}} $$) despite a low total exercise volume. Per the Fick principle, increased V˙O2peak$${\dot{\text{V}}}{\text{O}}_{2{\text{peak}}} $$ is attributable to increased peak cardiac output (Q˙peak$${\dot{{Q}}}_{\text{peak}} $$) and/or peak arterio-venous oxygen difference (a-vO2diff). There are limited and equivocal data regarding the physiological basis for SIT-induced increases in V˙O2peak$${\dot{\text{V}}}{\text{O}}_{2{\text{peak}}} $$, with most studies lasting ≤ 6 weeks.PurposeTo determine the effect of 12 weeks of SIT on Q˙peak$${\dot{{Q}}}_{\text{peak}} $$, measured using inert gas rebreathing, and the relationship between changes in Q˙peak$${\dot{{Q}}}_{\text{peak}} $$ and V˙O2peak$${\dot{\text{V}}}{\text{O}}_{2{\text{peak}}} $$.Methods15 healthy untrained adults [6 males, 9 females; 21 ± 2 y (mean ± SD)] performed 28 ± 3 training sessions. Each session involved a 2-min warm-up at 50 W, 3 × 20-s ‘all-out’ cycling bouts (581 ± 221 W) interspersed with 2-min of recovery, and a 3-min cool-down at 50 W.ResultsMeasurements performed before and after training showed that 12 weeks of SIT increased Q˙peak$${\dot{{Q}}}_{\text{peak}} $$ (17.0 ± 3.7 vs 18.1 ± 4.6 L/min, p = 0.01, partial η2 = 0.28) and V˙O2peak$${\dot{\text{V}}}{\text{O}}_{2{\text{peak}}} $$ (2.63 ± 0.78 vs 3.18 ± 1.1 L/min, p < 0.01, partial η2 = 0.58). The changes in these two variables were correlated (r2 = 0.46, p < 0.01). Calculated peak a-vO2diff also increased after training (154 ± 22 vs 174 ± 23 ml O2/L; p < 0.01) and was correlated with the change in V˙O2peak$${\dot{\text{V}}}{\text{O}}_{2{\text{peak}}} $$ (r2 = 0.33, p = 0.03). Exploratory analyses revealed an interaction (p < 0.01) such that Q˙peak$${\dot{{Q}}}_{\text{peak}} $$ increased in male (+ 10%, p < 0.01) but not female participants (+ 0.6%, p = 0.96), suggesting potential sex-specific differences.ConclusionTwelve weeks of SIT increased Q˙peak$${\dot{{Q}}}_{\text{peak}} $$ by 6% in previously untrained participants and the change was correlated with the larger 21% increase in V˙O2peak$${\dot{\text{V}}}{\text{O}}_{2{\text{peak}}} $$.