Background: Providing care for children with autism may negatively affect psychological, physical, and social aspects and quality of life among their family caregivers. Optimism is important in improving overall well-being by helping them have a positive attitude regarding their child's future health. Aim of the study: To assess the relationship between compassion fatigue and optimism among family caregivers of children with autism. Research design: A descriptive relational design. Setting: The study was applied at the autism unit in the faculty of postgraduate childhood studies affiliated with Ain Shams University. Subjects: A purposive sample of 200 family caregivers caring for children with autism. Data collection tool: 1) Structured interview questionnaire; 2) Clinical data sheet; 3) Professional Quality of Life Scale; and 4) Life Orientation Test-Revised scale. Results: The present study showed that 56.5% of the studied family caregivers of children with autism had an average level of total compassion fatigue and 47.5% of them had a low optimism level/ high pessimism. In addition, there was no statistically significant correlation between total compassion fatigue and optimism among caregivers of children with autism (P > 0.05). Conclusion: More than half of family caregivers of children with autism had an average level of total compassion fatigue, and slightly less than half of them had low optimism/high pessimism. There was no statistically significant correlation between total compassion fatigue and optimism among family caregivers of children with autism. Recommendations: Establishing an educational program for family caregivers of children with autism to raise their coping styles as well as enhance their psychological resilience to deal with burden of caregiving.