Normally, the brain maintains homeostatic control of body weight, successfully responding to changing energy needs. However, impaired appetite regulation, characterised by reduced appetite and body weight (cachexia-anorexia syndrome), occurs in many chronic disease states such as COPD, heart failure and cancer. Activin A (ActA), a member of the TGF-β family, is elevated in many chronic inflammatory conditions, including the aforementioned. Elevated ActA/B levels are also present, alongside cachexia, in our pancreatic cancer mouse model. Associations between ActA and cachexia symptoms have been observed, with heightened ActA levels correlating with weight loss, muscle degradation and mortality. As appetite regulation occurs in the brain and the activin receptor, ActRIIB, is located in brain regions associated with appetite control, we investigated whether ActA affects appetite or feeding-related behaviour. Mice were fasted overnight and food intake measured at multiple time points following ActA injection (varying doses). An ICV ActA dose of 0.15 ug and 0.5 ug (delivered into the lateral ventricle) suppressed refeeding within 1 hour. However this effect was not observed following intraperitoneal ActA injection. Furthermore, 0.15 ug ICV ActA also suppressed ghrelin-induced food intake, with the greatest effect observed at 1 hour post ActA injection. To assess sickness behaviour in response to ActA, we performed open field tests and behavioural barcoding analysis. No differences were observed in locomotor activity or in any of the 8 selected behaviours analysed, indicating ICV ActA does not produce malaise. Finally, ICV ActA was administered to assess c-fos immunoreactivity, a marker for neuronal activation, in brain regions involved in appetite control. Our findings reveal a role for ActA in appetite regulation, and pose the question of whether chronically high ActA levels in conditions such as cachexia may be responsible in part for facilitating appetite dysregulation.