The effect of low-intensity resistance exercise with external limb compression (100 [EC100] and 160 [EC160] mm Hg) on limb blood flow and venous blood gas-metabolite response was investigated and compared with that of high-intensity resistance exercise (no external compression). Unilateral elbow flexion muscle contractions were performed at 20% (75 repetitions, 4 sets, 30-second rest intervals) and 70% of 1-repetition maximum (1-RM; 3 sets, each set was until failure, 3-minute rest intervals). Precontraction brachial arterial blood flow (Doppler ultrasound) was reduced with EC100 or EC160 (56% and 39% of baseline value, respectively) compared with no external compression (control). At 20% 1-RM, brachial arterial blood flow increased after contractions performed with EC160 (190%), but not with the others. Decreases in venous oxygen partial pressure (P vO 2) and venous oxygen saturation (S vO 2) were greater during EC100 and EC160 than control (mean [SE]: P vO 2, 28 [3] vs 26 [2] vs 33 [2] mm Hg; S vO 2, 41% [5%] vs 34% [4%] vs 52% [5%], respectively). Changes in venous pH (pH v), venous carbon dioxide partial pressure (P vCO 2), and venous lactate concentration ([L −] v) were greater with EC160 than EC100 and/or control (pH v, 7.19 [0.01] vs 7.25 [0.01] vs 7.27 [0.02]; P vCO 2, 72 [3] vs 64 [2] vs 60 [3] mm Hg; [L −] v, 5.4 [0.6] vs 3.7 [0.4] vs 3.0 [0.4] mmol/L, respectively). Seventy percent 1-RM contractions resulted in greater changes in pH v (7.14 [0.02]), P vCO 2 (91 [5] mm Hg), and [L −] v (7.0 [0.5] mmol/L) than EC100 and EC160, but P vO 2 (30 [4] mm Hg) and S vO 2 (40% [3%]) were similar. In conclusion, changes in pH v, P vCO 2, and [L −] v, but not in P vO 2 and S vO 2, are sensitive to changes in relative, “internal” intensity of low-intensity muscle contractions caused by reduced blood flow (EC160) or high-intensity muscle contractions. Given the magnitude of the changes in pH v, P vCO 2, and [L −] v, it appears plausible that they may be involved in stimulating the observed increase in muscle activation via group III and IV afferents.