Nurses experience significant stress and emotional exhaustion, leading to burnout and fatigue. This study assessed how the nurses’ mood and fatigue evolves during their shifts, and the temporal factors that influence these phenomena. Performing a two-level design with repeated measures with moments nested into a person level, a random sample of 96 nurses was recruited. The ecological momentary assessment of demand, control, effort, reward, coping, and nursing tasks were measured in order to predict mood and fatigue, studying their current, lagged, and accumulated effects. The results show that: (1) Mood appeared to be explained by effort, by the negative lagged effect of reward, and by the accumulated effort, each following a quadratic trend, and it was influenced by previously executing a direct care task. By contrast, fatigue was explained by the current and lagged effect of effort, by the lagged effect of reward, and by the accumulated effort, again following quadratic trends. (2) Mood was also explained by problem-focused and emotion-focused coping strategies, indicative of negative mood, and by support-seeking and refusal coping strategies. (3) Fatigue was also associated with direct care and the prior effect of documentation and communication tasks. We can conclude that mood and fatigue do not depend on a single factor, such as workload, but rather on the evolution and distribution of the nursing tasks, as well as on the stress during a shift and how it is handled. The evening and night shifts seem to provoke more fatigue than the other work shifts when approaching the last third of the shift. These data show the need to plan the tasks within a shift to avoid unfinished or delayed care during the shift, and to minimize accumulated negative effects.