Background: Immunity plays an important role in PCNSL development. PCNSL predictive factors need to be improved. Objective: to evaluate the characteristics and predictive value of blood LIP in PCNSL patients. Methods: we prospectively analyzed blood LIP in all newly PCNSL referred to our institution between December 2013 and January 2020. LIP analysis was performed before rituximab and chemotherapy administration. The clinical, radiological, histological, biological and treatment data were retrospectively collected. Results: fifty-three patients were included with a median age of 69.7 (range 21.7-87.5). Median KPS was 60 (range 30-100). All patients presented with cerebral involvement, 13 (25%) with cerebrospinal fluid extension and 8 (15%) with ocular extension. Thirty-four patients (62%) benefited of steroid treatment at the time of LIP. Patients characteristics did not differ depending on steroid intake. Forty-eight patients (95%) benefited of polychemotherapy with high-dose methotrexate as first line treatment. We observed three (6%) lymphoproliferative syndromes on the LIP and 33 patients (64%) presented with one or several lymphopenias: 21 (40%), 24 (46%) and 9 (17%) NK, T and B lymphopenias respectively. Only 11 patients (21%) had normal LIP. Median CD4/CD8 ratio was 2.11 (range 0.54-9.11). This ratio was normal, low or high in 27%, 28% and 44% of patients respectively. The presence of steroids did not impact LIP results, including CD4 (p = 0.475) or CD8 (p = 0.726) rates and CD4/CD8 ratio (p = 0.727). Complete or partial responses, stable and progressive disease (PD) were observed in 24 (50%), 10 (21%), 4 (8%), and 10 (21%) patients respectively. CD4/CD8 ratio tended to be different between refractory (PD patients) and non-refractory patients (p = 0.077). A ROC curve analysis was performed with an AUC of 0.684 allowing the selection of a CD4/CD8 ratio cutoff of 1.97 with a sensibility, specificity, positive predictive value, and negative predictive value to identify refractory patients of 90%, 55%, 35% and 95% respectively. Median progression-free survival (PFS) and overall survival (OS) were 14.7 (95%CI: 6.5-22.9) and 43.2 (95%CI: 21.6-64.9) months, respectively. In multivariate analyses, adjusted by KPS, a CD4/CD8 ratio > 1.97 was associated with poor PFS (p = 0.043, HR = 3.32 [1.02-4.88]) and tended to be associated with worse OS (p = 0.064). Conclusions: LIP at baseline may predict refractory disease and exhibits a prognostic value in PCNSL patients.