Background: Fatigue increases throughout the working day and may lead to inefficiency and errors. Why do people become fatigued: because of the cumulative effects of energy expenditure (EE), the stress experienced or the accumulation of ego depleting demands? These questions were examined in nurses assessed in real time over two work shifts. Methods: 100 nurses completed electronic diaries which measured fatigue, tense arousal (stress) and work demand every 90 minutes. EE was measured continuously using the Actiheart system. The determinants of fatigue were tested in two ways by predicting fatigue from EE, stress and work demands: accumulated over a shift and for the previous two occasions (3 hours) using distributed lagged models with allowance for passage of time and concurrent values of determinants. Findings: Neither EE nor work demand predicted fatigue in either statistical model. However the accumulation of tense arousal (Beta .035, p<.002) and current levels (Beta .147 p<.001) did. Conclusion: Nurses do not get fatigued because of the energy they have expended nor the demands they have experienced but, in part, because, they have been stressed.