Background: Patients with juvenile idiopathic arthritis (JIA) often present with signs and symptoms suggestive of serious bacterial infection (SBI). However, it is a challenge to differentiate infectious from non-infectious presentation in routine clinical care. Procalcitonin (PCT) is a serum biomarker that is elevated in the setting of SBI, but whether it can reliably differentiate infection from disease flare in patients with JIA is unknown.1 We conducted a prospective cohort study to test the hypothesis that PCT levels will differ between active JIA, quiescent JIA, and bacteremic patients and healthy controls. Methods: From 10/16-4/18, consecutive children 6 months - 18 years of age with a) active untreated JIA (=>4 inflamed joints) b) quiescent JIA and c) healthy elective pre-surgical candidates were recruited from clinics at a musculoskeletal specialty hospital. JIA was defined according to ILAR criteria. Patients with active JIA despite treatment were excluded, to avoid confounding by treatment. Clinical data and serum samples from children with active and quiescent JIA meeting the same criteria were included from a prior study. Consecutive bacteremic patients were identified from an associated pediatric intensive care unit over the same period. No matching was performed. PCT as well as other common measures of inflammation were measured. Descriptive statistics and univariate logistic analyses were performed as appropriate using SAS version 9.4. The study was IRB approved. Results: Bacteremic patients were younger than patients in the other three groups (median age 2.1 vs. 14.0 years) and had a variety of infections. ESR, CRP, and PCT were all elevated in bacteremic patients in comparison to the other groups. ESR and CRP both had wide ranges that overlapped between groups; however, the PCT concentration exceeded 0.15ug/mL in 0 out of 27 patients with active JIA and 1 out of 32 patients with quiescent JIA, while it was <= 0.15ug/mL in only 1 bacteremic patient. PCT did not differ between patients with active and quiescent JIA. Conclusions: Our study indicates that serum ESR, CRP, and PCT levels are all biomarkers that can be used to distinguish SBI vs. active JIA at presentation. However, PCT is the most accurate, with the least overlap between patients with infection and non-infectious inflammatory arthritis. This finding can help clinicians direct therapy. However, PCT is not a useful biomarker to assess disease activity in JIA. Further studies are needed to assess whether measurement of serum PCT is useful in differentiating JIA flares from less severe infections.