Objective: The purpose of this study is to compare the thyroid hormone (TH) profile in male infertile subjects with normal and altered sperm parameters and assess its relationship with spermogram and reproductive hormones. Design: This cross-sectional study was conducted in Karachi from August 2017 till September 2018 on 376 male subjects between 25 and 55 years of age. The reference values for the “Normal Sperm Parameters” group was; sperm count (TC) >39 million per ejaculate, total sperm motility (Progressive and Non-progressive) >40% and normal morphology of ≥4%. Male subjects, having any one of the sperm parameters below the reference values comprised the group of “Altered Sperm Parameters”. The thyroid profile; Thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone, Thyroid Peroxidase antibodies (Anti-TPO) was estimated in addition to reproductive hormones Testosterone and Sex hormone binding globulin (SHBG). Independent sample T test and Analysis of Variance was applied for comparison of groups. Linear regression was performed and unadjusted and adjusted beta coefficient with 95% CI was reported. A P-value of <.05 was considered significant. Results: Two hundred and sixteen subjects had normal, whereas 160 had “Abnormal Sperm Parameters.” In “Normal Sperm Parameter” group; 206 (95.3%) were euthyroid while 10 (4.6%) were having subclinical hypothyroidism (SCH). Among the “Abnormal Sperm Parameters” group; eighty-seven (54%) subjects were euthyroid, sixty-two (38.75%) had SCH and eleven (6.8%) were having overt hypothyroidism. Testosterone and SHBG were significantly lower in “Altered Sperm Parameters” group as compared with “Normal Sperm Parameters” (P <.001 for both). Conclusion: A higher frequency of SCH, decreased levels of testosterone and SHBG was observed in the “Altered Sperm Parameters” group. The results establish relationship of disturbance in TH with alteration of sperm parameters and reproductive hormones thus contributing to male infertility.