Abstract Objectives To evaluate the thyroid hormone levels and infection markers in COVID-19 patients and compare them to those in non-COVID-19 patients with infection in a large retrospective dataset. Methods In this study, thyroid-stimulating hormone (TSH), thyroid hormones (free T3 and free T4), and several infection markers were reviewed. The study group was divided into three groups that had no thyroid-related disorders: control patients (Group 0; n=7,981), COVID-19 patients (Group 1; n=222), and non-COVID-19 patients with infection (Group 2; n=477). The data were assessed for correlation and group comparisons. Results There was a reduction in median (25th–75th percentile) fT3 levels in COVID-19 patients 4.17 pmol/L (3.46–4.85) compared to non-COVID-19 patients with infection 4.65 pmol/L (4.12–5.15), p<0.0001. We detected a negative correlation between fT3 and neutrophil-to-lymphocyte ratio (NLR) in Group 1 (r=−0.534) and Group 2 (r=−0.346) (p<0.0001), indicating a relatively stronger link between fT3 and NLR in COVID-19 patients than non-COVID-19 patients with infection. Additionally, the fT3 levels remained significantly different between study groups when the model was adjusted for age, gender, and infection markers. Conclusions COVID-19 and non-COVID-19 infections are associated with low fT3 levels, which likely represent the suppression of the hypothalamic-pituitary-thyroid axis from non-thyroidal illness syndrome.