Context: Drop jumps and high-intensity interval running are relevant training methods to improve explosiveness and endurance performance, respectively. Combined training effects might, however, be achieved by performing interval drop jumping. Purpose: To determine the acute effects of interval drop jumping on oxygen uptake ($\dot{\mathrm{V}}{\mathrm{O}}_2$)—index of cardioventilatory/oxidative stimulation level and peripheral fatigue—a limiting factor of explosiveness. Methods: Thirteen participants performed three 11-minute interval training sessions during which they ran 15 seconds at 120% of the velocity that elicited maximal $\dot{\mathrm{V}}{\mathrm{O}}_2$ ($\dot{\mathrm{V}}{\mathrm{O}}_2\text{max}$) (IT_run), or drop jumped at 7 (IT_DJ7) or 9 (IT_DJ9) jumps per 15 seconds, interspersed with 15 seconds of passive recovery. $\dot{\mathrm{V}}{\mathrm{O}}_2$ and the time spent above 90% of $\dot{\mathrm{V}}{\mathrm{O}}_2\text{max}$ (${}_{\mathrm{T}}\dot{\mathrm{V}}{\mathrm{O}}_2\text{max}$) were collected. Peripheral fatigue was quantified via preexercise to postexercise changes in evoked potentiated quadriceps twitch (ΔQT). Power output was estimated during IT_DJs using optical sensors. Results: All participants reached 90% of $\dot{\mathrm{V}}{\mathrm{O}}_2\text{max}$ or higher during IT_run and IT_DJ9, but only 11 did during IT_DJ7. ${}_{\mathrm{T}}\dot{\mathrm{V}}{\mathrm{O}}_2\text{max}$ was not different between IT_run and IT_DJ9 (145 [76] vs 141 [151] s; P = .92) but was reduced during IT_DJ7 (28 [26] s; P = .002). Mean ΔQT in IT_DJ9 and IT_DJ7 was not different (−17% [9%] vs −14% [8%]; P = .73) and greater than in IT_run (−8% [7%]; P = .001). No alteration in power output was found during IT_DJs (37 [10] W·kg⁻¹). Conclusion: Interval drop jumping at a high work rate stimulated the cardioventilatory and oxidative systems to the same extent as interval running, while the exercise-induced increase in fatigue did not compromise drop jump performance. Interval drop jumping might be a relevant strategy to get concomitant improvements in endurance and explosive performance.