Abstract Background Physical health decline may affect family members’ mental health by causing distress and, in case of functional impairments, need to provide care. We examined how diseases common in midlife but with different disease progression and level of impairment are associated with short-term and long-term changes in spousal depression. Methods We used Finnish total population register data from 2000-2019 to identify 91,849 men and 70,836 women aged 30-70 that experienced onset of severe diseases without cognitive impairment (myocardial infarction, prostate cancer, breast cancer), conditions with sudden onset and immediate impairment (stroke, traumatic brain injury) or progressive conditions with increasing impairment (Parkinson's disease, multiple sclerosis, dementia) while living with a spouse. We measured depression with antidepressant purchases and used fixed-effects linear probability models to examine spouses’ depression trajectories before and after onset of spousal disease Results Preliminary findings show that the onset of any type of spousal illness is associated with an increase in depression. Among men this increase is similar in magnitude irrespective of the type of spouse's illness, whereas among women the increase is smaller if the spouse is diagnosed with a disease without cognitive impairment. When the spouse is diagnosed with a progressive condition, female spouses’ depression increases more gradually, whereas a large immediate increase in depression follows sudden onset conditions. One year after diagnosis there are little changes in spousal depression. Conclusions Diseases common in midlife increase spouse's risk of depression around the time of diagnosis, and the effect appears persistent. Adequate support should thus be available to family members from the start of physical illness. When planning support to female spouses, the male spouse's cognitive impairment and associated care needs should be carefully evaluated. Key messages • Diseases common in midlife increase spouse's depression risk around the time of diagnosis, and the effect appears persistent. Support to spouses should be available from the start of illness. • Cognitive impairment of the male spouse seems to increase female spouse's depression particularly strongly, suggesting that caregiving help could be especially beneficial for women.