Chronic pain is defined as persistent or recurrent pain lasting longer than 3 months; the severity of pain can be rated in terms of intensity, pain-related distress, and functional impairment. Researches have shown an association between psychosocial factors, such as empathic ability, and the severity of pain. Cognitive-behavioral therapy (CBT) is the most common psychologic intervention for individuals with chronic pain. The aim of this study was to investigate the effect of CBT on empathy in chronic pain patients, examining especially gender differences. In total, 89 patients with severe chronic pain (46 men and 43 women) underwent 8 sessions of CBT over the course of 4 weeks. Self-reported clinical symptoms were measured at the beginning and end of the CBT. Empathy was measured using the interpersonal reactivity index, and pain severity was assessed using the short-form McGill pain questionnaire. A comparison of male and female patients before CBT indicated that females showed higher levels of empathy in response to affective issues and reported greater affective pain than males. A mixed analysis of variance revealed that female patients showed higher levels of empathy than did male patients, both before and after CBT. We also found significant relationships between affective pain and empathy for others' personal distress in all patients. These results suggest that the effectiveness of CBT may be affected by chronic pain patients' level of empathy. Although the evident result was not shown in this study, the present findings imply that female patients may formulate excellent therapeutic alliance in CBT intervention that can lead to a clinical benefit.