Background: Differentiating primary immune thrombocytopenia (ITP) from early stages of systemic lupus erythematosus (SLE)-associated thrombocytopenia (SLE-TP) is a challenge due to the lack of specific biomarkers. Objective: This study aimed to evaluate the difference level of serum interleukin-1 beta (IL-1β) in patients with ITP, SLE-TP, SLE without thrombocytopenia (SLE-NTP), and healthy controls to assess its potential utility as a diagnostic biomarker. Patients and methods: This case control study was conducted on 72 individuals aged 20-40 years. Patients were divided into four groups: ITP, SLE-TP and SLE-NTP, and healthy controls. Clinical, hematological, and immunological parameters were assessed. IL-1β levels were measured using ELISA. Results: IL-1β showed markedly elevated levels in SLE-TP (26.7±7.8) compared to ITP (4.61 ± 1.6 pg/ml) and controls (18.7 ± 3.8 pg/ml) (p < 0.001). IL-1β correlated positively with bleeding scores across all groups. IL-1β >10 showed 100% sensitivity and specificity in discriminating between ITP and SLE-TP (AUC=1.0, 95% CI: 1.0-1.0, p < 0.001) . Conclusions: IL-1β demonstrated exceptional potential as a diagnostic biomarker for differentiating ITP from SLE-TP, offering perfect discrimination at a threshold of >10 pg/ml. This finding could significantly improve diagnostic accuracy and treatment decision-making in clinical practice.