Abstract Ultra profound hypothermia (4 to 10°C) is an experimental method aiming at safely prolonging organ and total body preservation. For this purpose, Hypothermosol (HTS), an investigational acellular solution for blood substitution, was demonstrated to be beneficial in animal models undergoing cardiopulmonary bypass. We investigated the beneficial versus deleterious effects of cold preservation and the role of HTS on isolated coronary arteries (CA) during cold exposure, rewarming, and post-rewarming exposure to anoxia. Newborn lamb CA rings were studied using a tissue bath technique. CA were subjected to cold (7°C for 3 h) and treated with either Krebs' buffer (Krebs/hypothermia) or HTS (HTS/hypothermia) ( n = 15 each). A third group maintained at 37°C (Krebs/normothermia) ( n = 18) served as a time control. After rewarming (37°C), precontracted CA were exposed to anoxia. In Krebs/hypothermia a substantial hypercontraction (g) occurred during rewarming (1.21 ± 0.07) (mean ± SEM) but not in HTS/hypothermia (0.79 ± 0.03); P < 0.05. Precontraction force generated by indomethacin/U46619 was identical in all three groups. However, Krebs/hypothermia vessels demonstrated a significantly higher relative vasoconstriction (percentage) in the early (∼10 min) and late (30 min) anoxia exposure than the HTS/hypothermia and time control (119.5% ± 3.7 vs 109.5% ± 4.4 and 101.5% ± 3, and 71% ± 7.6 vs 38.9% ± 7 and 51.5% ± 5.9, respectively; P < 0.05). In conclusion, Ultra profound hypothermia promotes coronary vasoconstriction upon rewarming, which is detrimental to relaxant response to hypoxia. Both phenomena are alleviated by performing ultra profound hypothermia under HTS protection.