Parental care in Astatotilapia burtoni entails females protecting eggs and developing fry in a specialized buccal cavity in the mouth. During this mouthbrooding behavior, which can last 2–3 weeks, mothers undergo voluntary fasting accompanied by loss of body mass and major metabolic changes. Following release of fry, females resume normal feeding behavior and quickly recover body mass as they become reproductively active once again. In order to investigate the molecular underpinnings of such dramatic behavioral and metabolic changes, we sequenced whole-brain transcriptomes from females at four time points throughout their reproductive cycle: 2 days after the start of mouthbrooding, 14 days after the start of mouthbrooding, 2 days after the release of fry and 14 days after the release of fry. Differential expression analysis and clustering of expression profiles revealed a number of neuropeptides and hormones, including the strong candidate gene neurotensin, suggesting that molecular mechanisms underlying parental behaviors may be common across vertebrates despite de novo evolution of parental care in these lineages. In addition, oxygen transport pathways were found to be dramatically downregulated, particularly later in the mouthbrooding stage, while certain neuroprotective pathways were upregulated, possibly to mitigate negative consequences of metabolic depression brought about by fasting. Our results offer new insights into the evolution of parental behavior as well as revealing candidate genes that would be of interest for the study of hypoxic ischemia and eating disorders.