Background: Bipolar disorder is a chronic disorder that causes significant effects on the patient and exerts a significant care burden on caregivers. This study aimed to investigate the social support of patients, caregivers’ burden and their impact on the clinical course of the disease. Methods: The study included 85 patients with bipolar disorder type I and II (in the recovery phase of the disease) and their caregivers in the age range of 18 to 60 years. It was conducted in Shafa psychiatry Hospital in Rasht (Guilan, Iran, 2020). To assess social support and burden, patients and caregivers completed the Multidimensional Perceived Social Support Scale (MSPSS) and Caregiver Burden Inventory (CBI), respectively. Clinical variables were also obtained from patients’ medical records; Then ANOVA, MANOVA, Independent T-test were used to compare the data and Regression Analysis and Spearman correlation coefficient were used to find the relationships between variables. Results: It was showed that increasing patient social support is associated with reducing caregiver burden. Among the clinical variables, less social support and more caregiver burden were associated with longer duration of illness ( p < .0029, p < .012), decrease in last recurrence time ( p < .0013, p < .0001), increased number of hospitalizations ( p < .0001, r = −.43 and p < .0001, r = +.49), decreased response to treatment ( p < .0001, p < .0001), and reduced follow-up ( p = .001, OR = 1.12 and p = .001, OR = 0.95). Conclusion: The relationship between low social support and high caregiver burden and their significant effect on the disease course indicates a vicious cycle that affects patients, caregivers, and the clinical course of the disease. Therefore, it seems that interventions to break this cycle can change the situation in favor of patients and caregivers and improve the clinical course of the disease.