Mobility in older adults is essential to preserving their physical independence and health. Changes in mobility are related to cognitive, physical, and emotional factors, among others. We explored symptoms of depression as a mediator variable between chronic diseases and comorbidities and the outcomes of perceived health and life-space mobility in a convenience sample of 135 older Mexican adults. A cross-sectional design was used. Simple and multiple linear regression models were adjusted to verify the assumptions of mediation using Baron and Kenny's model. Chronic diseases and comorbidities served as independent variables in two separate models, perceived health and life-space mobility served as dependent variables, and depressive symptoms as the mediator variable. Results showed that perceived health and life-space mobility are affected by chronic diseases and comorbidities. However, when symptoms of depression enter the equation, the β coefficients decreased suggesting partial mediation. It is important to assess and treat depression symptoms in older adults rather than assuming that, at their age, depression is normal.