Objectives Whether or not the cardio-protective effect of β-adrenergic blockade is retained during resistance exercise has not been systematically evaluated. Therefore the purpose of this study was to measure selected cardiorespiratory responses to isometric exercise involving hand-gripping, single-leg extension, or double-leg dead-lift, under placebo (control), β1-selective (atenolol), and non-selective (propranolol) adrenergic blockade conditions. Design Eleven young male adults were evaluated in a randomized, double-blinded, repeated measures study design and performed all three exercise modalities at 30% of maximal voluntary contraction under placebo, atenolol and propranolol conditions. Methods Heart rate, systolic and diastolic blood pressure, rate-pressure product, oxygen uptake, cardiac output, stroke volume and total peripheral resistance were directly measured or calculated at rest and during the third minute of each of the three exercise modes. Results Irrespective of drug condition, a graded pressor response was observed going from rest to exercise so that rest \u3c handgrip \u3c leg extension \u3c dead-lift for heart rate, systolic and diastolic blood pressures, rate-pressure product and oxygen uptake (p \u3c 0.05 for all). Cardiac output only increased with the dead-lift mode of exercise (p \u3c 0.01). Importantly β-adrenergic blockade with either atenolol or propranolol similarly attenuated the rise in heart rate, and systolic blood pressure; thus rate-pressure product demonstrated a mode-of-exercise by drug interaction effect (p \u3c 0.001) with the greatest reductions seen with the dead-lift procedure. Conclusions The findings indicate that cardio-protection afforded by selective or non-selective β-blockade at rest is preserved during isometric exercise and even enhanced once heart rate increases above 100 beats min−1