Diffuse large B-cell lymphoma (DLBCL) is a rapidly growing malignant tumor, and chemotherapy is one of the treatments used to combat it. Although advancements of science and technology have resulted in more and more patients being able to receive effective treatment, they still face side effects such as fatigue and weakness. It is important to thoroughly investigate the factors that contribute to cancer-related fatigue (CRF) during chemotherapy.To explore the factors related to CRF, anxiety, depression, and mindfulness levels in patients with DLBCL during chemotherapy.General information was collected from the electronic medical records of eligible patients. Sleep quality and mindfulness level scores in patients with DLBCL during chemotherapy were evaluated by the Pittsburgh Sleep Quality Index and Five Facet Mindfulness Questionnaire-Short Form. The Piper Fatigue Scale was used to evaluate the CRF status. The Self-Rating Anxiety Scale and Self-Rating Depression Scale were used to evaluate anxiety and depression status. Univariate analysis and multivariate regression analysis were used to investigate the factors related to CRF.The overall average CRF level in 62 patients with DLBCL during chemotherapy was 5.74 ± 2.51. In 25 patients, the highest rate of mild fatigue was in the cognitive dimension (40.32%), and in 35 patients the highest moderate fatigue rate in the behavioral dimension (56.45%). In the emotional dimension, severe fatigue had the highest rate of occurrence, 34 cases or 29.03%. The CRF score was positively correlated with cancer experience (all P < 0.01) and negatively correlated with cancer treatment efficacy (all P < 0.01). Tumor staging, chemotherapy cycle, self-efficacy level, and anxiety and depression level were related to CRF in patients with DLBCL during chemotherapy.There was a significant correlation between CRF and perceptual control level in patients. Tumor staging, chemotherapy cycle, self-efficacy level, and anxiety and depression level influenced CRF in patients with DLBCL during chemotherapy.©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.