Health symptoms of mothers of adolescents and adults with fragile X syndrome (FXS; n = 112) were compared to a nationally-representative sample of mothers of similarly-aged children without disabilities (n = 230) as well as to a sample of mothers of adolescents and adults with autism spectrum disorders (ASD; n = 96). Health symptoms experienced in the previous 24 h were recorded during 8 consecutive days of a daily diary study. Both mothers of a son or daughter with FXS and mothers of a son or daughter with ASD had a higher proportion of days with headaches, backaches, muscle soreness, fatigue, and hot flashes than mothers of children without disabilities. Mothers of children with disabilities appear to be at particular risk for health problems, highlighting a need for comprehensive services for families across the lifespan.