Weightlifting is a common mode of exercise because of its positive effects on a host of physiological outcomes. However, the transient and extreme nature of the mean arterial blood pressure (MAP) response during and following resistance exercise, particularly whilst upright, will likely translate into fluctuations in middle cerebral artery blood flow velocity (MCAv). We examined the effect of resistance load and number of repetitions on the dynamic responses of MCAv during and following upright squatting exercise. Healthy resistance trained males (n = 12; mean ± SD: 26 ± 5 y; 94 ± 13 kg) completed 30, 60 and 90% of a predetermined 6 repetition maximum (RM) load, in a randomised order. Participants completed 2 or 6 repetitions of their 6 RM during two separate visits (order randomised between participants). Beat-to-beat MCAv and blood pressure, continuous end-tidal PCO2 and heart rate were measured. Peak MCAv and MAP during exercise, and nadir, recovery and peak following exercise were compared to a pre-exercise standing baseline period (1 min). There was no difference in average peak MCAv during exercise between loads (P = 0.737) or repetitions (P = 0.892). MAP was greater during the 60% compared to the 30% set (P = 0.015), and with 6 repetitions (P = 0.02 vs. 2 repetitions); specifically, 122 ± 9 vs. 135 ± 11 mm Hg for 2 and 6 repetitions at 30%, respectively; and 128 ± 13 vs. 143 ± 14 mm Hg for 2 and 6 repetitions at 60%, respectively. Only 3 participants had a satisfactory blood pressure trace for both 90% sets; MAP at this load peaked at 150 ± 2 and 176 ± 6 mm Hg mm Hg for 2 and 6 repetitions, respectively. Participants only performed a Valsalva manoeuvre during both 90% repetition sets, with an average mouth pressure of 43 ± 6 and 44 ± 10 mm Hg for the 2 and 6 repetition sets, respectively. Post-exercise MCAv reductions occurred via a selective, load-dependent (P < 0.001) decrease in diastolic MCAv. The 90% load produced the lowest MCAv nadir (-19 ± 6 cm/s, P < 0.001) and MAP nadir (-36 ± 10 mm Hg, P < 0.001) following exercise. Greater reductions in MCAv were seen at 30 and 60% loads following 6 repetitions (both P <0.05 vs. 2 repetition sets), but not for MAP (P= 0.59). The MAP nadir occurred later (13.3 ± 7.6 s) than MCAvmean nadir (6.7 ± 5.2 s) for all loads and repetitions (all P ≤ 0.05). Higher loads increased the time to MAP nadir (P = 0.05) but not MCAvmean nadir (P > 0.10). In summary, the combination of heavier loads and the Valsalva manoeuvre challenge cerebral autoregulatory processes and produce a greater reduction in MAP and subsequently MCAv immediately following dynamic upright resistance exercise. However, dynamic cerebral autoregulation begins to restore MCAv within the same time frame regardless of the magnitude of the drop in MCAv, and the magnitude and time course of the reduction in MAP.