Abstract Objectives Fetal/neonatal alloimmune thrombocytopenia (FNAIT) occurs when maternal IgG alloantibodies against paternal human platelet antigens (HPA) cross the placenta and cause the destruction of fetal platelets. The vast majority (up to 95%) of FNAIT cases are caused by antibodies against HPA-1a or HPA-5b antigens, while the remaining cases are usually due to antibodies against a variety of other HPA antigens. Cases of FNAIT due to anti-HLA antibodies are extremely uncommon and have only rarely been reported. We present a case of FNAIT suspected to be caused by anti-HLA class I alloantibodies. Methods The patient is a term infant boy born to a 32-year-old G2T2L2 mother. The mother had a previous diagnosis of Still disease (an adult form of systemic juvenile rheumatoid arthritis) but experienced complete resolution of symptoms and was off all treatment during the pregnancy. At birth, laboratory testing revealed isolated severe thrombocytopenia (platelet count 38,000/mcL) in an otherwise healthy-appearing infant. Results The infant had no evidence of bleeding, and testing for TORCH infection, sepsis, and DIC was negative. The maternal blood type was O positive. The maternal platelet count was normal. FNAIT was suspected and the infant was given two platelet transfusions from the same HPA 1a and 5b antigen-negative donor with no significant or sustained improvement in platelet count. Maternal platelet antibody testing subsequently revealed an absence of HPA antibodies, but anti-HLA class I alloantibodies were present. The infant was treated with three subsequent doses of IVIg with improvement in platelet count. No significant hemorrhage occurred. Conclusion HLA class I antibodies are commonly found in multiparous women but are not generally thought to cause significant fetal complications during subsequent pregnancies. This case suggests that, although rarely reported, HLA class I alloantibodies may be capable of causing FNAIT.