Systemic lupus erythematosus is an autoimmune disease that promotes chronic inflammation, with periods of activation and remission. Pain is commonly one of the first symptoms reported by patients with lupus. It interferes with patients’ quality of life, leading to a decrease in strength and difficulty in performing daily activities. Given the chronic nature of the disease, the high prevalence of pain and its negative impact on the quality of life of patients with lupus, the present literature review study aims to explain the pathophysiology of pain in systemic lupus erythematosus and the implications of the chronic process and contributing factors. During periods of systemic lupus erythematosus activity, pain is a significant symptom. Despite this, several studies show that severe pain can occur in patients with in mild to moderate disease activity. Also, in the early stages of the disease, the pain may be accentuated by the greater activity of the disease. However, even when advanced disease is under control, there can be comorbidities and accumulated damage that can also cause high levels of pain. This sensitivity is due to the overlap of primary, secondary, and tertiary pain pathologies, which feedback and make this symptom one of the main concerns of patients with lupus. Understanding the pathophysiology of pain in systemic lupus erythematosus, as well as its chronification and contribution factors, is essential to identify effective therapeutic alternatives in these patients at each stage of pain pathology (primary, secondary, and tertiary).