Aim Subclinical hypothyroidism (SCH) with TSH less than (10µIU/ml) is a common finding discovered during routine thyroid function testing. Thyroxine substitution and its benefits to alleviate dyslipidemia and oxidative stress (OS) markers at this stage are a matter of debate.Material and Methods This study aimed to investigate the influence of thyroxine substitution on lipid profile and oxidative stress markers in newly diagnosed SCH subjects. The study included a total number of 50 newly diagnosed, (20 treated and 30 untreated) SCH subjects aged 20-50 years with (TSH < 10 μIU/ml) and FT4 levels in the normal range. Patients on medications that could cause thyroid hormone dysfunction, diabetes mellitus and current or pregnancy during the last two years were excluded. Serum TSH, T3, T4, FT4, Anti-thyroid peroxidase (TPO) antibodies, Total cholesterol (TC), High-density lipoprotein cholesterol (HDL), Triglycerides (TG), low-density lipoprotein cholesterol (LDL), ischemia-modified albumin (IMA) were determined in all subjects at baseline and after nine months.Results After Thyroxine replacement, a significant decrease in TSH, LDL, IMA and an increase in FT4 was observed. The decrease in TC was not statistically evident. There was no significant change in T3, T4, TG, HDL, after treatment. The untreated group showed an insignificant increase only in TSH.Conclusion Thyroid substitution therapy has a favorable influence on lipid profile and oxidative stress where it particularly reduced LDL and IMA.Key Words: Subclinical hypothyroidism, L-Thyroxine, Lipids, IMA, oxidative stress