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Background Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are chronically exposed to disease uncertainty and high stress, and their psychological trait of intolerance of uncertainty is strongly associated with poor health outcomes, but existing research lacks comprehensive analyses based on multilevel ecosystems. Objective To analyze the current situation and influencing factors of intolerance of uncertainty in patients with AECOPD under the perspective of health ecology, and to provide reference for formulating targeted intervention strategies. Methods From November 2024 to June 2025, patients with AECOPD in the Respiratory and Critical Care Medicine Center of Xinjiang Uygur Autonomous Region People's Hospital were conveniently selected as the survey objects. The Intolerance of Uncertainty Scale-12, the Acceptance and Action Questionnaire-Ⅱ, the COPD Knowledge Questionnaire, and the Perceived Social Support Scale were used to conduct a cross-sectional survey. Pearson correlation analysis was used to explore the correlations among psychological flexibility, health literacy, social support and intolerance of uncertainty. Multiple linear regression analysis was adopted to investigate the influencing factors of intolerance of uncertainty in patients with AECOPD. Results A total of 360 questionnaires were distributed in this study. 342 valid questionnaires were recovered, with an effective recovery rate of 95.0%. 342 patients with AECOPD had a total score of intolerance of uncertainty (32.2±7.1). The scores of psychological flexibility, health literacy and social support were (24.7±8.6), (6.9±2.4), (54.7±11.8). The results of the correlation analysis indicated that the score of intolerance of uncertainty was positively correlated with the score of psychological flexibility (r=0.648, P<0.001), and negatively correlated with the scores of health literacy and social support (r=-0.548, -0.643, P<0.001). Multiple linear regression analysis showed that the number of comorbidities (B=1.057, 95%CI=0.552-1.563), number of hospital admissions (B=1.646, 95%CI=0.409-2.882), regular exercise (B=1.670, 95%CI=0.551-2.789), average monthly medication cost (B=2.962, 95%CI=1.623-4.300), psychological flexibility (B=0.151, 95%CI=0.065-0.238), health literacy (B=-0.754, 95%CI=-0.992 to -0.517), and social support (B=-0.128, 95%CI=-0.188 to -0.068) were the main influencing factors of intolerance of uncertainty in patients with AECOPD (P<0.05). Conclusion The intolerance of uncertainty of AECOPD patients is at a moderately high level, and their intolerance of uncertainty is influenced by the multilevel factors. Comprehensive interventions should be carried out for AECOPD patients according to the patient's condition and from multiple perspectives, such as psychological, family, and social.