Background: Atrial fibrillation (AF) and coagulation disorder, two common complications of sepsis, are associated with the mortality. However, the relationship between early coagulation disorder and AF in sepsis remains elusive. This study aimed to evaluate the interaction between AF and early coagulation disorder on mortality. Methods: In this retrospective study, all data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Septic patients with coagulation tests during the first 24 h after admission to intensive care units (ICUs) meeting study criteria were included in the analysis. Early coagulation disorder is defined by abnormalities in platelet count (PLT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) within the first 24 h after admission, whose score was defined with reference to sepsis-induced coagulopathy (SIC) and coagulopathy. Patients meeting study criteria were divided into AF and non-AF groups. Results: In total, 7,528 septic patients were enrolled, including 1,243 (16.51%) with AF and 5,112 (67.91%) with early coagulation disorder. Compared with patients in the non-AF group, patients in the AF group had higher levels of INR and APTT (P < 0.001). Multivariable logistic regression analyses showed that stroke, early coagulation disorder, age, gender, congestive heart failure (CHF), chronic pulmonary disease, renal failure, and chronic liver disease were independent risk factors for AF. In addition, AF was related to in-hospital mortality and 90-day mortality. In the subgroup analysis stratified by the scores of early coagulation disorder, AF was associated with an increased risk of 90-day mortality when the scores of early coagulation disorder were 1 or 2 and 3 or 4. Conclusion: In sepsis, coagulation disorder within the first 24 h after admission to the ICUs is an independent risk factor for AF. The effect of AF on 90-day mortality varies with the severity of early coagulation disorder.