Background: Subclinical hypothyroidism (SCH) is defined as high TSH and normal thyroxine. Data on the effects of early substitution by levothyroxine on psychophysical health in SCH are still not consistent enough to support its introduction. Methods: Clinical parameters, biochemical data and quality of life (Short Form 36 questionnaire) were measured before the intervention and 3 months after the euthyroid state had been achieved in SCH patients. Results: Significant reduction in body weight (p = 0.030), systolic and diastolic blood pressure (p = 0.024, p = 0.019), homocysteine (p< 0.001), leukocytes and neutrophils (p = 0.011, p = 0.001), INR (p = 0.049), K levels (p = 0.040, p= 0.013), HbA1c (p= 0.001), fasting insulin (p< 0.001) and insulin resistance measured by HOMA index (p< 0.001), lipid parameters (total cholesterol (p< 0.001), LDL-cholesterol (p< 0.001), triglycerides (p = 0.007), apoB (p = 0.022), Lp(a) (p< 0.001), LDL/HDL (p = 0.008), LAP (p = 0.04) and apoB/apoA1 ratios (p< 0.023)), TSH (p< 0.001) and tAbs p< 0.001) was recorded. Frequency of fatty liver (20% to 2.9%, p = 0.016), hyperlipidemia (85% to 65.7%, p = 0.001) and metabolic syndrome (34.3% to 2.9%, p = 0.070) significantly decreased. A statistically significant positive association was found between the average dose of levothyroxine and changes in physical functioning (r= 0.391, p = 0.020), vitality (r= 0.393, p = 0.020), mental health (r= 0.374, p = 0.027) and overall dimensions of mental health (r= 0.376, p = 0.026). With increasing doses of levothyroxine, the previously listed scores of SF 36 grew (r= 0.296, p = 0.084). Conclusions: Early substitution of SCH improved the many clinical and biochemical parameters related to cardiovascular risk. Quality of life was also improved, and correlated only with thyroxine doses suggesting an indirect relationship between the degree of hypothyroidism and quality of life.