The influence of handling, salinity, temperature, parasitism, and gender on the immune responses (reactive oxygen species (ROS) production and coelomic amoebocyte concentration (CAC) of the starfish Asterias rubens was investigated in experimental conditions. Additionally, a year-round monthly survey in two distant sites was conducted in order to understand which of these factors most influences the immunity of A. rubens in field conditions. All considered factors, except gender and handling stress, influenced the studied immune responses of A. rubens in experimental conditions. Amoebocyte ROS production was increased at low salinity and at the lowest temperature tested (6°C). Amoebocyte concentration in the coelomic fluid was increased in starfish infested by the ciliate Orchitophrya stellarum. However, among all these factors, only temperature could be linked with the variability in ROS production measured in the field during the monthly survey. The variability in amoebocyte concentration in the field does not seem to be linked to any of the factors considered in this study; it appears to reflect mostly an inter-individual variation rather than seasonal fluctuations. Recommended periods and indicative values of immune responses are proposed for field studies using A. rubens.