Children and adolescents infected by HIV through mother-to-child transmission are at high risk of developing premature cardiovascular diseases due to dyslipidemia, insulin resistance and low-grade chronic inflammation. The aim of the pilot study was to verify the effect of a playful exercise program on cardiovascular, morphological, metabolic, fitness, and quality of life outcomes. A non-randomized clinical trial consisting of 24 sessions of playful aerobic and resistive exercises was applied to 10 children and adolescents living with HIV from Florianopolis, Brazil. The following variables were obtained before and after the program: fasting total cholesterol, HDL-c, LDL-c, triglycerides, glucose, C-reactive protein, blood pressure, common carotid artery intima-media thickness (CCA-IMT), flexibility, muscular endurance, aerobic fitness, anthropometry, and measured quality of life. After the intervention, a decrease in systolic blood pressure (-6.8 mmHg, 6.6%; p = 0.019) and CCA-IMT (-60.0 µm, 12.2%; p = 0.002) was observed after 24 sessions. There was an increase in upper-limb muscular endurance (+3.3 rep.min -1 , 63.5%; p = 0.002), flexibility (+5.7 cm, 26.0%; p = 0.001), and quality of life (+10.4 points, 27.5%; p = 0.003). In our sample of children and adolescents living with HIV, a short-term exercise program was associated with improvement in cardiovascular risk, fitness, and quality of life.