Background: This study aimed to investigate the clinical manifestations and risk factors for 28-day mortality in patients with stress cardiomyopathy (SC) in the intensive care unit (ICU). Methods: This retrospective study was carried out from April 2015 to March 2021. Fifty-five patients in the ICU were diagnosed with SC. Two patients were excluded due to a history of atrial fibrillation (AF), and 53 patients were enrolled in the study. Baseline demographics and clinical characteristics were collected, and the 28-day mortality rate was calculated. Multivariate and univariate logistic regression analyses were used to determine the significant predictors of 28-day mortality. Results: Of the 53 patients, almost half (47.17%) were male. The most common stress trigger was sepsis (37.74%). Due to sedation and tracheal intubation, 49.06% of SC patients were unable to express their symptoms, and only 3.77% of patients presented with chest pain. The proportion of patients with complications of systolic heart failure and cardiogenic shock was 77.36% and 39.62%, respectively. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score when patients were admitted into the ICU was 21.17 +/- 8.41, and the Sequential Organ Failure Assessment (SOFA) score at diagnosis of SC was 9.30 +/- 4.56. Eighteen (33.96%) SC patients had new-onset AF while in the ICU. The 28-day mortality rate in patients with SC in the ICU was 64.15%. Univariate analysis found that 5 variables [SOFA score at diagnosis of SC, estimated glomerular filtration rate (eGFR) <60 mL/min at diagnosis of SC, maximum norepinephrine dose, new-onset AF, and systolic heart failure] were correlated with 28-day mortality in patients with SC in the ICU. Multivariate logistic regression analysis suggested SOFA score at diagnosis of SC (P=0.042), eGFR <60 mL/min at diagnosis of SC (P=0.027), and new-onset AF (P=0.043) as independent predictors of 28-day mortality. Conclusions: Male patients with SC were relatively more common in the ICU than in the cardiology unit. Sepsis was a common stress trigger. The 28-day mortality rate was very high. The SOFA score and eGFR <60 mL/min at diagnosis of SC and new-onset AF may have influenced patients' short-term prognosis.