Background <p>Thrombocytopenia (platelet count &lt; 150 × 10⁹/L) is a common complication in critically ill patients and is associated with adverse outcomes. However, its incidence, dynamic changes, and relationship with systemic inflammation and mortality specifically in patients after cardiac arrest remain insufficiently investigated.</p> Methods <p>We conducted a single-center retrospective cohort study of adults with return of spontaneous circulation (ROSC) after cardiac arrest (January 2016 to May 2024). Serial platelet counts and inflammatory biomarkers (procalcitonin, ferritin) were tracked in all patients. 12 plasma cytokines were assessed in a subset of patients (<i>n</i> = 18) on day 3 after ROSC. Longitudinal platelet dynamics were analyzed using linear mixed-effects models, and the association of thrombocytopenia severity with mortality was assessed via time-dependent Cox regression.</p> Results <p>Of 245 patients achieving ROSC, 198 were included in the final analysis. Thrombocytopenia occurred in 74.2% (95% CI, 67.5–80.1) of patients after ROSC. Linear mixed-effects models revealed significantly different temporal platelet patterns between survivors and non-survivors (<i>p</i> &lt; 0.001), with counts remaining persistently low in non-survivors. Inverse trends were observed between platelet counts and procalcitonin/ferritin; In the cytokine subgroup (<i>n</i> = 18), this extended to IL-6, IL-8, IL-10, and IL-12p70 (<i>p</i> &lt; 0.05). A dose-response relationship existed between thrombocytopenia severity and mortality, with a graded risk increase for severe (HR 4.10, 95% CI 1.82–9.22, <i>p</i> = 0.001) and very severe thrombocytopenia (HR 8.83, 95% CI 3.16–24.65, <i>p</i> &lt; 0.001).</p> Conclusion <p>Thrombocytopenia is highly prevalent after cardiac arrest and exhibits distinct dynamic patterns between survivors and non-survivors. It is associated with inflammatory activation and serves as an independent predictor of increased mortality risk.</p>