This study aimed to investigate if moderate to vigorous physical activity (MVPA) and aerobic fitness are associated with cardiovascular risk factors in HIV+ children and adolescents. Sixty-five children and adolescents (8 to 15 years) provided minutes of MVPA measured by accelerometers and peak oxygen uptake (peak VO₂) by breath-by-breath respiratory exchange. Cardiovascular risk factors were characterized by body fat, blood pressure, total cholesterol, HDL-c, LDL-c, triglycerides, glucose, insulin, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α) and carotid intima-media thickness. Results indicated that higher MVPA was associated with lower values of total (β =  −3.566) and trunk body fat (β = −3.495), total cholesterol (β = −0.112) and LDL-c (β = −0.830). Likewise, higher peak VO₂ was associated with lower total (β = −0.629) and trunk body fat values (β = −0.592) and levels of CRP (β = −0.059). The physically active participants had lower total cholesterol (−24.4 mg.dL⁻¹) and LDL-c (−20.1 mg.dL⁻¹) compared to participants judged to be insufficiently active. Moreover, participants with satisfactory peak VO₂ showed lower total (−4.1%) and trunk (−4.3%) body fat, CRP (−2.3 mg.L⁻¹), IL-6 (−2.4 pg.mL⁻¹) and TNF-α (−1.0 pg.mL⁻¹) compared to low peak VO₂ peers. High levels of MVPA and aerobic fitness may prevent developing of cardiovascular risk factors in children and adolescents HIV+.