Abstract Background Information on welfare cost of patients with schizophrenia and spouses is limited. Aim The main aim of this study to investigate factual societal mean annual costs per individual during 5 years before and after the initial diagnosis of schizophrenia. Method A register-based cohort study of 12 227 patients with incident schizophrenia (International Classification of Diseases, Tenth Revision F20-F20.99) with spouses and 48 907 matched controls in Denmark during 2002–2016. Results The total annual costs of health care and lost productivity were Euro 43 561 higher for patients with schizophrenia and health care costs and costs of lost productivity were increased during 5 years before the initial diagnosis. The total annual direct health care and indirect costs of lost productivity were Euro 21 888 higher for spouses to patients with schizophrenia than spouses of individuals with no diagnosis of schizophrenia. Also before initial diagnosis, health care costs and lost productivity were increased among spouses of patients with schizophrenia. Conclusion Patients with schizophrenia differed from the general population with respect to all included costs. The study documented a significant burden on spouses. The excess health care costs of schizophrenia are further increased by psychiatric and somatic comorbidity, and the societal costs are 4–10 times higher than chronic neurological disorders such as epilepsy and multiple sclerosis. Early onset of schizophrenia implies that patients are affected before finishing school and before entrance to labor market. Cost savings could be achieved by investments in preventive interventions reaching young people’s needs; in initiatives to reduce hospital admissions caused by medication side effects, substance misuse, and lifestyle factors; and in occupational training.