Introduction <p>Serum sickness, a type III hypersensitivity reaction, can arise from various triggers such as vaccines, anti-venoms, and certain medications, particularly monoclonal antibodies. Rituximab, a monoclonal antibody targeting CD20 on B-cells, is known to induce a subtype of this reaction called rituximab-induced serum sickness, which primarily affects those with rheumatologic diseases.</p> Case presentation <p>A 34-year-old Mexican–American female patient with focal segmental glomerulosclerosis was treated with rituximab for concomitant immunoglobulin G4-related disease. After her third infusion, she developed a rash, myalgias, arthralgias, and proteinuria, leading to a diagnosis of rituximab-induced serum sickness, which resolved with a prednisone taper.</p> Conclusion <p>Serum sickness should be considered as a potential differential diagnosis in patients exhibiting nonspecific systemic symptoms and dermatologic manifestations following exposure to a triggering factor, such as a newly administered monoclonal antibody medication. This is the first known case of rituximab-induced serum sickness in the context of immunoglobulin G4-related disease.</p>