Hemophagocytic lymphohistiocytosis (HLH) is a highly fatal syndrome characterized by excessive abnormal activation of the immune system. Fever is the most encountered clinical feature and is found in 100% of HLH cases (Al-Samkari & Berliner, 2018) Fever patterns can be an important clinical clue in certain diseases but have not been described in HLH. We report a 74-year-old Caucasian female patient who presented with fever, fatigue, and dyspnea on exertion of 2 months duration. On examination, she was found to be febrile, hypoxic, and disoriented. Initial laboratory workup was significant for normocytic anemia (6.3 g/dl) with severely elevated Ferritin (1501 µg/dL). Infectious and autoimmune workup was negative. Full body CT scan was negative for malignancy or lymphadenopathy but showed mild splenomegaly. The hospital course was complicated by worsening respiratory status despite empiric antibiotic treatment. She was noted to have persistent daily fever spikes in the early hours of the morning. This prompted workup for HLH which revealed rising serum ferritin, hypertriglyceridemia, elevated soluble IL-2 and low NK cell activity receptors, fulfilling the criteria of HLH. Bone marrow aspirate revealed clonal CD20 positive lymphocyte diagnostic of DLBCL as the trigger for HLH. The patient was started on HLH protocol and mini R-CHOP protocol with marked improvement in her symptoms and anemia. Little is known about the patterns of fever in HLH patients. Before this case, two other case reports described quotidian fever in HLH (Kouides et al., 2021; Henter et al., 2007). interestingly both were cases of secondary HLH. This case illustrates the possible association between HLH and quotidian fever and proposes the possibility of quotidian fever being a clinically important clue to secondary causes of HLH. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal