Disclosed herein are methods of treating a hepatitis E viral infection comprising administering to a human subject in need thereof a therapeutically effective amount of the compound sofosbuvir, also known as (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate. Some methods further comprise concomitantly administering ribavirin to the subject. In some methods, the treatment is ribavirin-free. In some methods, the subject is immunocompromised. In some methods, the subject is pregnant.