Although it is suspected that anxiety modifies the clinical presentation of autism in fragile X syndrome (FXS), neuropsychiatric co-morbidity profiles of these two disorders have not been extensively studied. The National Fragile X Survey was completed for 1,027 males with FXS, for whom yes/no information regarding the presence of several disorders is provided. Although the survey exhibited limited depth and lacked validation by standardized measures, this exploratory study was conducted to take advantage of the data as an opportunity for identifying future lines of inquiry. We addressed the following questions: (i) how do the co-morbidity profiles of FXS males with both autism and anxiety compare to those without anxiety?; (ii) do individuals with autism exhibit specific co-morbidity profiles compared to FXS males with anxiety only, or without either autism or anxiety?; (iii) how do co-morbidity profiles in children ages 3–11 differ from profiles of individuals >12 years? The group with autism and anxiety reported the highest prevalence of attention problems, hyperactivity/impulsivity, self-injurious behavior and aggressiveness. In addition, the lowest prevalence rates of these conditions were often observed in non-anxious groups regardless of autism status. Overall, this exploratory analysis generated several hypotheses for further study: (i) anxiety increases the severity of autism in FXS, particularly through additional behavioral abnormalities; (ii) some neuropsychiatric and behavioral conditions (i.e., attention problems, hyperactivity/impulsivity, aggressiveness) are primarily related to comorbid anxiety, not autism; (iii) prevalence of behavioral abnormalities increases with age. Future studies evaluating these hypotheses should incorporate validated neurobehavioral assessments, and control for cognitive level. © 2014 Wiley Periodicals, Inc.