Survival sepsis campaign recommends that vasopressor therapy is required to maintain mean arterial pressure (MAP) ≥ 65 mmHg. However, the absolute maximum dose of vasopressor is difficult to determine. Herein, we report 2 cases of severe skin necrosis after high dose vasopressor infusion to maintain the recommended MAP in septic shock. In our first case, norepinephrine 1.0－2.0 μg/kg/min and vasopressin 0.03－0.1 U/min were infused for 5 days; in the second case, dopamine 10－20 μg/kg/min and norepinephrine 0.25－2.5 μg/kg/min were infused for 7 days. Severe ischemic skin lesions, which required amputations, developed in both cases. The clinical appearance of the skin lesions in the 2 cases was different because of the unique distribution of target receptors for different vasopressors. Thus, when high dose vasopressors are required to achieve recommended MAP, extra vigilance is required. Further studies for dose adjustment are needed.