Infections of the thyroid gland are rare. Its innate resistance to infections can be attributed to its unique anatomical features and rich blood supply. High clinical suspicion is required as a delay in diagnosis can lead to significant morbidity and mortality. Major pathogens include the Gram-positive Staphylococcus aureus and Streptococcus species; however, Gram-negative organisms have been found especially in immunocompromised hosts. We present a rare case of acute suppurative thyroiditis (AST) secondary to Escherichia coli (E. coli) infection in a woman known to be infected with human immunodeficiency virus (HIV).