Background: Breast cancer survivors (BCSs) often face long-term complications, with upper-limb lymphedema and cancer-related fatigue (CRF) being challenging. This study aimed to investigate the relationship between upper-limb lymphedema and fatigue among BCSs. Method: This cross-sectional study was performed on 102 BCSs, of which 31 (30.4%) had breast cancer-related lymphedema. Duration, stage, and excess volume were considered as indicators of breast cancer-related lymphedema severity. QoL was measured using the EORTC QLQ-C30. The score of the fatigue symptom scale was used based on EORTC QLQ-C30 for CRF assessment. Also, the brief fatigue inventory was used to measure the severity of fatigue among participants. Results: The mean fatigue symptom scale and brief fatigue inventory scores were 37.90 +/- 24.59 and 3.69 +/- 1.25, respectively. The mean fatigue symptom scale was significantly different among BCSs with BMI <= 25 and BMI > 25 (29.59 +/- 24.49 vs. 41.51 +/- 23.88, p = 0.026). Also, the mean brief fatigue inventory was significantly different among BCSs with the number of dissected lymph nodes (LNs) <= 5 and > 5 (3.52 +/- 1.18 vs. 4.08 +/- 1.34, p = 0.042). Additionally, women with breast cancer-related lymphedema had significantly higher scores of fatigue symptom scale and brief fatigue inventory (46.59 +/- 27.12 vs. 34.11 +/- 22.56, p = 0.03, and 4.75 +/- 1.21 vs. 3.22 +/- 0.96, p = 0.001, respectively). Except for a weak correlation between BMI and fatigue symptom scale and brief fatigue inventory (r: 0.279, p = 0.004, and r: 0.313, p = 0.001, respectively), there was no other significant relationship between CRF and study variables such as breast cancer-related lymphedema duration, stage, and excess volume. Meanwhile, fatigue symptom scale and brief fatigue inventory were significantly correlated with global health and functional scale scores of EORTC QLQ-C30. The ROC curve which models the diagnostic efficacy for fatigue symptom scale showed an AUC of 0.634 (p = 0.034, 95% CI: 0.510-0.759), while the ROC curve which models the diagnostic efficacy for brief fatigue inventory showed an AUC of 0.821 (p < 0.001, 95% CI: 0.735-0.908). Conclusion: This study highlighted that while breast cancer-related lymphedema was associated with increased CRF, the severity of lymphedema did not significantly correlate with CRF. Additionally, CRF might be an indicator of breast cancer-related lymphedema among BCSs.