Purpose: Whether thrombocytopenia in critically ill patients accounts for a bystander of severity or drives specific complications is unclear. We addressed the effect of thrombocytopenia on septic shock, with emphasis on intensive care unit (ICU)-acquired bleeding, infections and thrombotic complications. Materials and methods: A retrospective (2008–2019) single-center study of patients with septic shock. Thrombocytopenia was assessed over the first seven days and was defined as severe (nadir <50 G/L), mild (nadir 50–150 G/L) and relative (30% decrease with nadir >150 G/L). Outcomes were ICU mortality and ICU-acquired complications defined by severe bleeding, infections and thrombotic events during the ICU stay. Results: The study comprised 1024 patients. Severe, mild and relative thrombocytopenia occurred in 33%, 40% and 9% of patients. The in-ICU mortality rate was 27%, independently associated with severe thrombocytopenia. ICU-acquired infections, hemorrhagic and thrombotic complications occurred in 27.5%, 13.3% and 11.6% of patients, respectively. Patients with severe, mild or relative thrombocytopenia exhibited higher incidences of bleeding events (20.3%, 15.3% and 14.4% vs. 3.6% in non-thrombocytopenic, p < 0.001), infections (35.2%, 21.9% and 33.3% vs. 23.1% in non-thrombocytopenic, p < 0.001) and thrombotic events (14.6%, 10.8% and 17.8% vs. 7.8% in non-thrombocytopenic, p = 0.03). Only severe thrombocytopenia remained independently associated with increased risk of bleeding. Conclusions: Severe thrombocytopenia was independently associated with ICU mortality and increased risk of bleeding, but not with infectious and thrombotic events.