Background: In addition to the hallmark cognitive and functional impairments mounting evidence indicates that schizophrenia is also associated with an increased risk for the development of secondary complications, in particular cardio-metabolic disease. This is thought to be the result of various factors including physical inactivity and the metabolic side effects of psychotropic medications. Therefore, non-pharmacological approaches to improving brain health, physical health, and overall well-being have been promoted increasingly. Methods: We report on the health-related physical fitness (body composition, blood pressure, heart rate, and aerobic fitness) and lipid profile of persons living with schizophrenia and effective means to address the challenges of exercise training in this population. Results: There was a markedly increased risk for cardio-metabolic disease in 13 persons living with schizophrenia (Age = 31 ± 7 years) including low aerobic fitness (76% ± 34% of predicted), reduced HDL (60% of cohort), elevated resting heart rate (80% of cohort), hypertension (40% of cohort), overweight and obesity (69% of cohort), and abdominal obesity (54% of cohort). Individualized exercise prescription (3 times/week) was well tolerated, with no incidence of adverse exercise-related events. The exercise adherence rate was 81% ± 21% (Range 48%–100%), and 69% of the participants were able to complete the entire exercise training program. Exercise training resulted in clinically important changes in physical activity, aerobic fitness, exercise tolerance, blood pressure, and body composition. Conclusion: Persons living with schizophrenia appear to be at an increased risk for cardio-metabolic disease. An individualized exercise program has shown early promise for the treatment of schizophrenia and the various cognitive, functional, and physiological impairments that ultimately affect health and well-being.