Experimental studies have shown that both cadmium (Cd) and lead have potent endocrine disrupting activity. However, studies on whether these heavy metals disrupt thyroid system in humans, especially in general populations with low levels of exposure, are sparse. The study analyzed 6,231 participants aged 20 and older with measurements from 2007–2010 of the National Health and Nutrition Examination Survey (NHANES) to investigate whether whole blood Cd and lead level are associated with serum thyroid hormones measures. Our study suggests that thyroid function may be disrupted by both Cd and lead exposures in the general population and the specific roles of Cd and lead exposure on thyroid axis may differ by sex. However, the mechanisms by which these heavy metals may disrupt thyroid system function in general population needs to be further investigated.