The aim of this study was to evaluate the lipid profile of patients with different degrees of hypothyroidism and the effect of levothyroxine replacement in subclinical hypothyroidism (SH). Initially, a cross-sectional study was performed with 226 participants [SH = 133 participants, manifest hypothyroidism (MH) = 23 participants, and euthyroidism (EU) = 70 participants]. The mean levels of atherogenic lipid variables were greater in MH than in SH and were greater in SH than in EU, although the differences between SH and EU did not reach statistical significance. The SH subgroup with greater serum thyrotropin (TSH) levels and that with positive antithyroperoxidase antibodies (TPO-Ab) had greater levels of triglycerides and of the atherogenic index Apo B/Apo A. A positive correlation exists between serum TSH and total cholesterol (rs = 0.167; P = 0.006), triglycerides (rs = 0.219; P < 0.001), and ApoB levels (rs = 0.205; P < 0.001). Eleven patients who received levothyroxine (L-T4) treatment and 15 patients who received placebo were reevaluated 1 year after TSH adjusted intervention. A fall in atherogenic variables was observed in the L-T4-treated group, with significance for total cholesterol (-20.0 vs +16.1 mg/dL in the placebo group) and LDL-c (-21.7 vs +17.2 mg/dL). We concluded that SH leads to an intermediary lipid profile between euthyroid individuals and that found in manifest hypothyroidism and that a significant lipid profile improvement occurred 1 year after L-T4 replacement therapy.