This study aimed to assess the effects of a 2-month lifestyle modification trial on cardio-metabolic abnormalities and C-reactive protein (CRP) among obese adolescents with metabolic syndrome [phenotypically obese metabolically abnormal (POMA)] and obese adolescents without a cardio-metabolic disorder [phenotypically obese metabolically normal (POMN)], as well as in normal-weight adolescents with at least one cardio-metabolic disorder [phenotypically normal metabolically obese (PNMO)]. The study comprised 360 adolescents assigned in three groups of equal number of POMN, POMA and PNMO. They were enrolled in a trial consisting of aerobic activity classes, diet and behaviour modification, and were recalled after 6 months. Overall, 94.7% of participants completed the 2-month trial, and 87.3% of them returned after 6 months. The mean CRP was not significantly different between the POMA and PNMO groups, but was higher than in the POMN group. After the trial, body mass index (BMI) and waist circumference (WC) decreased in obese participants, and the mean body fat mass decreased in all groups. At 2 months, the mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and CRP decreased in the POMA and PNMO groups. After 2 and 6 months, the decrease in mean TC, LDL-C, TG, CRP and systolic blood pressure was greater in the POMA than in the POMN group. The magnitude of decrease in CRP correlated with that of BMI, WC, fat mass, TG, TC and LDL-C. Lifestyle modification programmes for primordial/primary prevention of chronic diseases would be beneficial at the population level and should not be limited to obese children.