A baroreflex mechanism may explain hypertensive hypoalgesia. At rest, arterial baroreceptors are stimulated during the systolic upstroke of the pressure pulse wave. This study examined the effects of naturally occurring variations in baroreceptor activity during the cardiac cycle on an objective measure of pain, the nociceptive flexion reflex (NFR). Two interleaved up–down staircase procedures determined separate NFR thresholds during systole and diastole in 36 healthy, normotensive young adults. On odd-numbered trials, the sural nerve was stimulated electrocutaneously at R + 300 ms whereas on even-numbered trials, stimulation was delivered at R + 600 ms. The NFR threshold was higher at R + 300 ms than R + 600 ms. In contrast, stimulus intensity ratings did not differ between R + 300 ms and R + 600 ms. Stimulation of baroreceptors by natural increases in blood pressure during the systolic phase of the cardiac cycle was associated with dampened nociception.