One previous study indicated the significance of trait self-compassion in psychological well-being and adjustment in people with chronic pain. Higher-frequency heart rate variability (HF-HRV) was found to be closely associated with self-compassion and pain coping. The current study was therefore designed to investigate the relationship between self-compassion and experimental pain as well as the impact of HF-HRV. Sixty healthy participants provided self-reported self-compassion and underwent a cold pain protocol during which HF-HRV was evaluated. Results demonstrated a dual relationship between self-compassion and pain, dependent on the level of HF-HRV during pain exposure. Specifically, self-compassion was associated with lower pain in the condition of higher HF-HRV, while there was an inverse relationship between self-compassion and pain when HF-HRV was lower. Our data indicate the significance of HF-HRV in moderating the association between self-compassion and experimental pain.