The distinction between foot and ankle wound healing complications as opposed to infection is crucial for the appropriate and efficacious allocation of antibiotic therapy. Multiple reports have focused on the diagnostic accuracy of different inflammatory markers, however, mainly in the diabetic population. To evaluate the diagnostic accuracy of white cell count (WCC) and C-reactive protein (CRP) as diagnostic tools for this distinction in the non-diabetic cohort. Data was reviewed from a prospectively maintained Infectious Diseases Unit database of 216 patients admitted at Leicester University Hospitals-United Kingdom with musculoskeletal infections over the period between July 2014 and February 2020 (68 mo). All patients with confirmed diagnosis of diabetes were excluded while only those with confirmed microbiological or clinical diagnosis of foot or ankle infection were included in our study. For the included patients, we retrospectively retrieved the inflammatory markers (WCCs and CRP) at the time of presentation. Values of CRP 0-10 mg/L and WCC 4.0-11.0 × 109/L were considered normal. After exclusion of patients with confirmed diabetes, 25 patients with confirmed foot or ankle infections were included. All infections were confirmed microbiologically with positive intra-operative culture results. 7 (28%) patients with osteomyelitis (OM) of the foot, 11 (44%) with OM of the ankle, 5 (20%) with ankle septic arthritis and 2 (8%) patients with post-surgical wound infection were identified. Previous bony surgery was identified in 13 (52%) patients, either a corrective osteotomy or an open reduction and internal fixation for a foot or ankle fracture with the infection developing on top of the existing metalwork. 21 (84%) patients did have raised inflammatory markers while 4 (16%) patients failed to mount an inflammatory response even with subsequent debridement and removal of metal work. CRP sensitivity was 84%, while WCC sensitivity was only 28%. CRP has a relatively good sensitivity in the diagnosis of foot and ankle infections in non-diabetic patients, whereas WCC is a poor inflammatory marker in the detection of such cases. In presence of clinically high level of suspicion of foot or ankle infection, a normal CRP should not rule out the diagnosis of OM.