Background: Systemic sclerosis (SSc) is a progressive autoimmune connective tissue disease. Platelets to lymphocytes (PLR) and platelets to haemoglobin ratios (PHR) are emerging biomarkers used in the assessment of activity and severity of various autoimmune diseases. This study was designed to clarify the association of PLR and PHR with SSc disease activity and its different manifestations. Method: A cross-sectional study involved sixty SSc patients. Demographic, clinical data and investigations were done. Results: PLR and PHR were correlated positively with ESR (r=0.351, p=0.003*), (r=0.620, p=0.000**), CRP (r=0.417, p=0.001*), (r=0.305, p=0.018**) and SSc activity index (r=0.292, p=0.024*), (r=0.359, p=0.005*). PLR and PHR were highly significantly related to digital ulcerations, musckeloskeletal, and pulmonary manifestations. Also, they had a significant relation to ground glass abnormalities on HRCT, mild restriction in pulmonary function tests and anti-scleroderma-70 antibodies. The cutoff value for PLR was 107.8 with high sensitivity 97.9% and specifity 92.3%, area under the curve (AUC=0.723, P 0.015) on receiver operating characteristic curve (ROC). PHR AUC (0.799, P .001), cut value was 23.5 at 95.7% sensitivity and 84.6% specifity. Conclusion: PLR and PHR were significantly related to digital ulcerations, musculoskeletal, and pulmonary manifestations and can be considered as predictive biomarkers for the assessment of SSc disease activity and severity.