Abstract Background Severely ill patients might develop an alteration of their immune system called post-aggressive immunosuppression. We sought to assess the risk of ICU-acquired infection and of mortality according to the absolute lymphocyte count at ICU admission and its changes over 3 days. Methods Adults in ICU for at least 3 days with a shock or persistent low blood pressure were extracted from a French ICU database and included. We evaluated the impact of the absolute lymphocyte count at baseline and its change at day 3 on the incidence of ICU-acquired infection and on the 28-day mortality rate. We categorized lymphocytes in 4 groups: above 1.5 × 103 cells/µL; between 1 and 1.5 × 103 cells/µL; between 0.5 and 1 × 103 cells/µL; and below 0.5 × 103 cells/µL. Results A total of 753 patients were included. The median lymphocyte count was 0.8 × 103 cells/µL [0.51–1.29]. A total of 174 (23%) patients developed infections; the 28-day mortality rate was 21% (161/753). Lymphopenia at admission was associated with ICU-acquired infection (p