Abstract Zebrafish (Danio rerio Hamilton) are increasingly used as model to study effects of chronic stress on brain and behaviour. In rodents unpredictable chronic stress (UCS) has a stronger effect on physiology and behaviour during the active phase than the resting phase. Here, we applied UCS during day-time (active phase) for 7 and 14 days or during the night-time (resting phase) for 7 nights in an in-house reared Tuebingen Long-Fin (TLF) zebrafish strain. Following UCS, inhibitory avoidance learning was assessed using a 3-day paradigm where fish learn to avoid swimming from a white to a black compartment where they will receive a 3V shock. Latencies of entering the black compartment were recorded before training (day 1; first shock) and after training on day 2 (second shock) and day 3 (no shock, tissue sampling). Fish were sacrificed to quantify whole-body cortisol content and expression levels of genes related to stress, fear and anxiety in the telencephalon. Following 14 days UCS during the day, inhibitory avoidance learning decreased (lower latencies on day 2 and 3); minor effects were found following 7 days UCS. Following 7 nights UCS inhibitory avoidance learning decreased (lower latency on day 3). Whole-body cortisol levels showed a steady increase compared to controls (100%) from 7 days UCS (139%), 14 days UCS (174%l) to 7 nights UCS (231%), suggestive of an increasing stress load. Only in the 7 nights UCS group expression levels of corticoid receptor genes (mr, gr-alpha, gr-beta) and of bdnf were increased. These changes are discussed as adaptive mechanisms to maintain neuronal integrity and prevent overload, and indicative of a state of high stress load. Overall, our data suggest that stressors during the resting phase have a stronger impact than during the active phase. Our data warrant further studies on the effect of UCS on stress-axis related genes, especially gr-beta; in mammals this receptor has been implicated in glucocorticoid resistance and depression.