Background: Pain, anxiety, and fatigue are known to significantly influence labor; however, the interacting relationships among the three symptoms have not been empirically shown. Purpose: The aim of this study was to investigate the interrelationships among intrapartum pain, anxiety, and fatigue relative to the mode of delivery, with or without epidural analgesia (EDA). Methods: A prospective, repeatedmeasures designwas adopted, and women with uncomplicated pregnancies at term (N = 186) were enrolled. Self-reported visual analog scales were used to assess pain, anxiety, and fatigue during the four phases of labor, as determined by cervical dilation (e.g., Phase 1 = 2Y4 cm,Phase 2 = 4Y6 cm, Phase 3 =10 cm, and Phase 4 = immediately after delivery of the placenta). Of the 186 participants, 48 received EDA when their cervical dilation was 3Y4 cm. Results: Throughout the process of labor, pain, anxiety, and fatigue were significantly correlated, no matter whether participants had received EDA, especially during Phases 1 and 3. For the participants undergoing EDA, the level of fatigue decreased more slowly than the levels of pain and anxiety. The participants who received EDA had significantly greater pain and fatigue in Phase 1 of labor than those who did not receive EDA. Mode of delivery was correlated with age, parity, and pain level in Phase 2 of labor and anxiety level in Phase 2 of labor. Conclusions/Implications for Practice: Intrapartum pain, anxiety, and fatigue were strongly interrelated. Intrapartum pain management (EDA) led to a significant decline in anxiety and fatigue. Furthermore, fatigue accumulated during the course of labor and was not easily diminished. These findings provide a reference for maternity nurses to develop strategies for managing multiple symptoms.