Lipopolysaccharide (LPS) is a potent endotoxin, which produces “sickness behaviours” including loss of weight, loss of interest in food and decreased exploration. LPS has also been shown in some studies to cause deficits in various learning and memory abilities, while in others these LPS-induced learning impairments have been attributed to performance-related deficits rather than learning deficits per se. Here, we use the novelty-preference paradigm, a task that minimises performance-related factors such as motivation, in an attempt to extract and examine the effects of LPS on spatial learning. In addition, some studies have indicated that the anti-inflammatory cytokine Interleukin-10 (IL-10) can alleviate some of the symptoms induced by LPS. Here, we also examine the effect of IL-10 on feeding, motor and learning behaviours. We demonstrate that a single injection of LPS does produce a lack of interest in food and weight loss; LPS, however, does not impair habituation in the noveltypreference paradigm. Furthermore, co-injection of IL-10 with LPS does not attenuate the LPS-induced effects of weight loss and lack of food intake. Interestingly, a single injection of IL-10 produces abnormal patterns of exploration, a general increase in activity and abnormal patterns of habituation.