The study aimed to document the utility of the absolute number of natural killer cells as a biomarker in paediatric orbital myositis (OM). Extracted data from four children with OM included demographics, laboratory values, imaging and treatment response. Stored sera (-80°C) were tested for IgG4 levels in three cases and antibody to Coxsackie B in two cases. Their first symptom was at 14.4±1.2 years (mean±SD). At diagnosis three had creatine phosphokinase (CPK) of 97.3±44.2, aldolase of 8.5±2.8 (n=2), alanine aminotransferase (ALT) of 13±2.8 (n=2) and aspartate aminotransferase (AST) of 21.3±2.9. IG4 level was 87.7±66 (normal=8-89 mg/dL); two sera (patients 1and4) were positive (>1:8 dilution) for anti-Coxsackievirus antigen B5. The CD3-CD16+CD56+ natural killer absolute count was 96.7±28.7 (lower limit of normal=138), increasing to 163±57.2 with disease resolution in three patients. The fourth patient was followed elsewhere. CT showed involvement of bilateral superior oblique, lateral rectus or the left medial rectus muscles. Treatment included intravenous methylprednisolone, methotrexate (n=2) and other immunosuppressants. Paediatric OM disease activity was associated with initially low absolute CD3-CD16+CD56+ natural killer cell counts, which normalised with improvement. We speculate (1) infection, such as Coxsackie B virus, may be associated with paediatric OM; and (2) the absolute count of circulating CD3-CD16+CD56+ natural killer lymphocytes may serve as a biomarker to guide medical therapy.