Schizotypal traits and cognitive disturbances are known to be present in first-degree relatives of people with schizophrenia. However, there is little understanding of how these endophenotypes are related to each other. We explored the nature of this relationship in individuals with schizophrenia, their full siblings, community controls, and their siblings. All participants were assessed in the domains of working memory, attention, episodic memory, and executive function, as well as in their level of positive, negative, and disorganization symptoms. Schizophrenia probands were significantly impaired on all cognitive domains, as compared with the other 3 groups, and displayed the highest levels of positive, negative, and disorganization symptoms. Proband siblings performed significantly worse than controls on tasks of working memory, episodic memory, and executive function, and they displayed significantly more positive and negative symptoms as compared with controls. Poorer task performance across all 4 cognitive domains was most strongly correlated with increased negative symptoms. Mediation analyses revealed that working memory, episodic memory, and executive function deficits partially mediated increases in negative symptoms among proband siblings. Negative symptoms fully mediated deficits in working memory and episodic memory but only partially mediated deficits in executive function. Results suggest that there is a complex relationship between cognitive and clinical factors in this high-risk population.