Abstract Background: Caregiving is schizophrenia is challenging and burdensome. Aim and Objectives: The study aimed to know the sociodemographic predictors of care burden and psychological distress in schizophrenia. Materials and Methods: The present study was a cross-sectional descriptive study. A total sample of 540 caregivers of persons with schizophrenia was selected, using purposive sampling from the outpatient Department of LGBRIMH, Tezpur, Assam. The study was approved by the IEC of LGBRIMH, Tezpur. Statistical analysis was done using SPSS version 23.0. Results: The mean age of patients and their caregivers was 35.6 ± 13.4 and 37.7 ± 12.4 years, respectively. Moderate to severe level of care burden was present in male caregivers (55.6%). Severe level of stress, anxiety, and depression was present in majority of the male respondents (42.5%, 43.2%, and 49.0%, respectively) who were the primary caregivers (41.2%, 40.8%, and 48.9%, respectively), married (41.2%, 37.7%, and 48.1%, respectively), belonging to rural background (43.8%, 43.2%, and 48.5%, respectively), educated till primary level (42.6%, 44.6%, and 58.3%, respectively), mostly unemployed (49.2%, 47.5%, and 50.8%, respectively) belonging to lower socioeconomic background (46.6%, 49.2%, and 48.0%, respectively), and with a history of mental illness in the family (41.6%, 40.7%, and 48.0%, respectively). Extremely severe level of stress (57.1%), with severe level of anxiety and depression (41.7%, 52.8%), was present in majority of the caregivers having nuclear family type condition. Marital status, occupation, family income, and type of caregiving contribute significantly to the prediction of care burden (F [14,525] =11.6, P = 0.001), whereas, caregiver’s gender, education, and, patient’s onset of illness contribute significantly to the prediction of psychological distress among caregivers (F [14,525] =5.31, P = 0.001). Conclusion: Psychosocial intervention is the need of the hour.