Background: Septic arthritis, also known as infectious arthritis, results from an acute invasion of the joint space by microorganisms that release endotoxins and trigger cytokine release and neutrophil infiltration. This invasion may happen through the hematogenous spread, contiguous spread from another locus of infection, or direct inoculation to a joint. Other causes include iatrogenic from arthrocentesis or arthroscopy. Bacteria, Mycobacterium, and fungi are the most common culprits. Patients typically present with joint pain, swelling, and fever. The condition is associated with increased morbidity and mortality and thus requires prompt diagnosis and treatment.

Case Report: We reported the case of a 55-year-old female with a past medical history of Klippel-Trenaunay Syndrome (KTS), Escherichia Coli (E. Coli) bacteremia seven years ago, chronic deep venous thrombosis, and type 2 diabetes mellitus who presented with chief complaints of left knee swelling and tenderness. She had Escherichia Coli septic arthritis. She underwent incision and drainage of the infected joint and started on four weeks of antibiotics.

Conclusion: This case is essential as it reports a rare cause of septic arthritis. Gram-negative bacilli account for only 10% to 15% of all cases of septic arthritis and are a growing concern. Moreover, it discusses a practical approach to treating this condition. Patients with KTS are susceptible to recurrent bouts of cellulitis. However, there is no report of increasing the risk of septic arthritis, which could have been the predisposing factor in our patient.