<p>Levofloxacin is a fluoroquinolone antibiotic widely used to treat various bacterial infections. It exhibits a broad spectrum of activity against Gram-positive and Gram-negative bacteria, making it a valuable therapeutic option in clinical practice. However, like other medications, levofloxacin is associated with potential adverse reactions. This case report is to document and analyze the occurrence of lower limb edema as a possible adverse reaction to levofloxacin injection. A 54-year-old Asian male was admitted to the hospital on February 25, 2023, due to chest tightness, chest pain, chills, and fever. Physical examination findings included diminished breath sounds in the right lower lung, clear breath sounds in the left lung, and no abnormalities in the abdomen, liver, spleen, spine, or limbs. Blood tests showed elevated white blood cell count, neutrophil percentage, and high-sensitivity C-reactive protein. The patient received intravenous levofloxacin treatment on the day of admission (February 25, 2023); however, on February 27, 2023 (the 3rd day after initiating levofloxacin treatment), he developed eyelid swelling and lower limb edema, which prompted the discontinuation of levofloxacin. This case report highlights a rare adverse reaction to levofloxacin injection, namely the development of lower limb edema. The report underscores the importance of recognizing and promptly managing medication-induced edema in clinical practice. Healthcare professionals should be aware of the potential risks associated with levofloxacin injection and consider it as a possible cause of lower limb edema in patients receiving this medication. Further research and pharmacovigilance are necessary to enhance our understanding of the incidence, mechanisms, and optimal management strategies for levofloxacin injection-induced lower limb edema.</p>