Background Epinephrine administered during cardiopulmonary resuscitation (CPR) is associated with severe post‐resuscitation myocardial dysfunction. We previously demonstrated that therapeutic hypothermia reduced the severity of post‐resuscitation myocardial dysfunction caused by epinephrine; however, the relationship between myocardial adrenoceptor expression and myocardial protective effects by hypothermia remains unclear. Methods and Results Rats weighing between 450 and 550 g were randomized into 5 groups: (1) normothermic placebo, (2) normothermic epinephrine, (3) hypothermic placebo, (4) hypothermic epinephrine, and (5) sham (not subject to cardiac arrest and resuscitation). Ventricular fibrillation was induced and untreated for 8 minutes for all other groups. Hypothermia was initiated coincident with the start of CPR and maintained at 33±0.2°C for 4 hours. Placebo or epinephrine was administered 5 minutes after the start of CPR and 3 minutes before defibrillation. Post‐resuscitation ejection fraction was measured hourly for 4 hours then hearts were harvested. Epinephrine increased coronary perfusion pressure during CPR (27±6 mm Hg versus 21±2 mm Hg P <0.05). Post‐resuscitation myocardial function was impaired in the normothermic epinephrine group compared with other groups. The concentration of myocardial cAMP doubled in the normothermic epinephrine group (655.06±447.63 μmol/L) compared with the hypothermic epinephrine group (302.51±97.98 μmol/L; P <0.05). Myocardial β 1 ‐adrenoceptor expression decreased with normothermia cardiac arrest but not with hypothermia regardless of epinephrine. Conclusions Epinephrine, administered during normothermic CPR , increased the severity of post‐resuscitation myocardial dysfunction. This adverse effect was inhibited by intra‐arrest hypothermia resuscitation. Declined cAMP with more preserved β 1 ‐adrenoceptors in hypothermia‐resuscitated myocardium is associated with improved post‐resuscitated myocardial function in vivo.