While it has been well-established that individuals with tic disorders, the most severe of which is Tourette syndrome (TS), experience high rates of social rejection, the psychological mechanism by which this occurs remains unaddressed. In the present research, two models – each based on previously researched theories of social rejection – are proposed to explain and test this mechanism: the Behavioural Immune System (BIS), which posits that individuals presenting with atypical features elicit social rejection by evoking disease concepts in observers, and the Interpersonal Depression Model (IDM), which is premised on a desire to avoid negative mood states that arise through interacting with people who display them. In Study 1, previous research investigating the link between conspicuous facial skin disease and disease concepts was replicated using the BIS, and extended to include social rejection of Tourette syndrome, in a 3 target Condition (Skin Disease, Tourette syndrome, Control) moderated mediation design. In Study 2, the relation between social rejection and Tourette syndrome was examined alongside a Depression condition in a replication/extension of the IDM in a 3 target condition (Depression, Tourette syndrome, Control) mediation design. Participants for Studies 1 and 2 were recruited through both the undergraduate participant pool of an Ontario university and Amazon’s Mechanical Turk. Results, overall, did not support either the BIS or the IDM as explanatory models for social rejection of TS; however, aspects of both models were supported, most notably the positive relation between negative evoked emotions and social rejection. The implications of these findings for both future research and clinical practice are discussed.