Rituximab (RTX) causes B‑cell depletion by binding to the CD20 antigen. A less well-known adverse drug reaction of RTX is late-onset neutropenia (LON), which occurs approximately 6 months after treatment initiation. As clinical management, regular differential blood cell counts should be performed during RTX treatment. Besides a watch-and-wait strategy, supportive administration of granulocyte colony-stimulating factor (G-CSF) can be discussed for acute LON episodes. Re-exposure to RTX after LON has occurred is generally considered acceptable after diligent benefit-risk evaluation and thorough patient information. In this case series, we would like to present 2 cases of rheumatology patients with severe LON after RTX administration.