The purpose of the current investigation is to evaluate the relationship between erythrocyte indices and thyroid function in a general population from the southern region of Saudi Arabia. In a cross-sectional study conducted on 3,007 subjects examined associations among erythrocyte indices, thyroid-stimulating hormone, and free thyroxine. The average age of the population was 48.40±0.261 years, ranging from 13 years to 90 years, and the most represented age group was <50 years. Thyroid dysfunction was observed in 8.41% of the study population, and the most common thyroid dysfunction was subclinical hypothyroidism followed by clinical hyperthyroidism. Most erythrocyte indices were significantly lower in the hypothyroidism group (both primary and subclinical) in comparison to the euthyroid group stratified by gender. According to our investigation, microcytic hypochromic anemia and normocytic normochromic anemia were detected in patients with hypothyroidism. Furthermore, females with subclinical hypothyroidism had a significantly higher prevalence of anemia than male population.