The aim of this prospective cohort study was to assess whether the prevalence of chronic disease of one spouse would be associated with a change in depressive symptoms of the other spouse and whether this relationship varies by immigrant status. Negative binomial regression was used to calculate risk ratios from a matched sample of 553 husbands and 553 wives aged 65 years or older of Mexican Americans. Overall, prevalence of chronic disease of one spouse was associated with change in high depressive symptoms for the other spouse. When the results were stratified by immigrant status, respondents born in the US exhibited higher risk of depressive symptoms associated with the chronic conditions of their spouse, while foreign born respondents did not exhibit higher risk for depressive symptoms. These findings highlight how immigrant status and the marital relationship may be related to chronic disease and depression.