Biological hydrogen production is being evaluated for use as fuel, since it is a promising substitute for carbonaceous fuels owing to its high conversion efficiency and high specific energy content. The microalga Chlamydomonas reinhardtii when grown under sulfur-deprived conditions, switches the metabolism toward the production of hydrogen. A better understandings of physiological and biochemical changes occurring during each phases of the process, represents a prerequisite to enhance the hydrogen output. The aim of this work was to study whether the activation of enzymes of the antioxidant defense system, such as catalase (CAT), ascorbate peroxidase (APOX) and guaiacol peroxidase (GPOX), takes place during the entire process of hydrogen production by C. reinhardtii CC 124. Kinase activities present in the crude protein extract and the mitotic specific ones associated with CKS1 protein were assayed to determine how the conditions leading to hydrogen production affected the activities of mitotic and growth associated kinases. We present evidences that oxidative stress enzymes are active during the entire hydrogen production process, besides their activities are higher in the anoxic phase. Stress condition during hydrogen photoproduction provoked at least partial cell cycle arrest leading to block of mitosis and cell division. These findings are in line with the known down-regulation or block of cell cycle related processes in stressed or starved cells. Copyright (C) 2015, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.