Organisms are often forced to acclimate to changing environmental temperature. Temperature compensation mechanisms have been reported, which enable organisms to minimize some of the temperature related effects. To investigate this process, zebrafish (Danio rerio) were acclimated to a control (26 °C), an increased (34 °C) or a decreased (18 °C) temperature for 4, 14 and 28 days. In general, warm acclimation depleted energy stores and decreased the condition factor, while cold acclimation increased both. The energy parameters as well as the transcriptional responses (investigated using printed 15k microarrays and real time PCR) indicated that warm acclimation was particularly stressful. However, after 28 days of warm acclimation, energy stores had recovered from the initial depletion. This could have been facilitated by the observed downregulation of transcripts involved in catabolic processes. Transcriptional regulation seemed to be an important means of coordinating the temperature compensation process. We could distinguish an early response which was independent of the direction of the temperature change and a direction specific long-term response. The early response was characterized by the upregulation of defence mechanisms, tissue regeneration and hemopoiesis. In the long-term response there was a strong emphasis on compensating for the altered metabolic rate as well as cell structure and replacement.