OBJECTIVE To assess the metabolic effects of primary hypothyroidism (PHT) on the leptin (LP), adiponectin (ADP) level and leptin adiponectin ratio (LAR), with identification of the beneficial effects of L-thyroxine (LT4) therapy on these parameters. METHODS This case-control study was conducted at the Department of Pharmacology, College of Medicine, Mustansiriyah University, Baghdad, Iraq, from July to October 2019. This study included 62 PHT patients, of whom 27 were newly diagnosed and 35 were on LT4 therapy. There were 28 healthy controls. Anthropometric, lipid and pressure profiles were evaluated along with estimation of TSH, T3, T4, LP and ADP serum levels. SPSS version 20.00 was used for data analysis. RESULTS LP serum level did not significantly differ among the three groups (P=0.23), however, ADP serum level was higher in patients with PHT on LT4 therapy (77.48±9.97ng/dL) as compared to the newly diagnosed patients without LT4 (66.21±7.67ng/dL), and controls (71.40±10.72), (P=0.01). Moreover, LAR was higher in non-treated PHT (1.29±0.18) as compared to the controls (1.13±0.14), (95%CI=0.0568 to 0.2632, P=0.001) and treated PHT (1.04±0.16), (95%CI=-0.3480 to -0.1520, P=0.001). On the other hand, no significant difference was detected between healthy controls and treated PHT patients (95%CI=-0.1871 to 0.0071, P=0.07). CONCLUSIONS PHT is associated with poor cardio-metabolic profile and high LAR. ADP but not LP, mainly affected in patients with PHT. However LAR is better than ADP and LP in reflecting the underlying PHT-induced cardio-metabolic derangements. LT4 replacement therapy improves cardio-metabolic profile, ADP and LP serum levels with significant amelioration of LAR in PHT patients.