Introduction: Hemolytic anemia is an infrequent complication of brown recluse spider bites (BRSB). This study aims to better understand the characteristics of patients with brown recluse spider-associated hemolytic anemia. Methods: We performed a retrospective chart review in the University of Missouri-Columbia healthcare system’s electronic medical record (EMR) from October 2015 through June 2023 using ICD codes for BRSB. We excluded all patients without evidence of anemia or who had clinical features not consistent with a BRSB. Results: Thirty-seven patients met the inclusion criteria. Sixty-one percent of patients were discharged and then returned with worsened symptoms. Eighty-one percent of patients developed constitutional symptoms. Severe anemia was associated with systemic symptoms, darkened urine, and typical hemolysis laboratory findings. Increased transfusion requirements were associated with higher nadir LDH. Of note, there was an increase in total bilirubin and/or LDH one day prior to a significant drop in Hgb (>= 2.0 g/dL) in 75% and 83% of patients, respectively. Forty-one percent of patients required blood transfusions. Conclusion Patients who developed hemolytic anemia commonly had multiple visits prior to the detection of their hemolysis. Constitutional symptoms, typical hemolysis lab findings, increased LDH levels, and an increase in total bilirubin and/or LDH should raise concern for the development of severe anemia even if Hgb levels are presently normal or mildly decreased. Early testing of LDH and total bilirubin may help risk stratification in these patients