Immune Effects of Low-dose Naltrexone in ME/CFS

Inclusion Criteria: 1\. Meet the 1994 Case Definition criteria for CFS (assessed through semi-structured interview and the DePaul University Fatigue Questionnaire): * Criteria: * Severe chronic fatigue ≥6 consecutive months not due to ongoing exertion or other medical condition associated with fatigue; * Fatigue interferes with daily activities and work; * Reports ≥4 symptoms that started with or after the fatigue, from: * Post-exertion malaise \>24 hours * Unrefreshing sleep * Short-term memory or concentration impairment * Muscle pain * Joint pain without swelling or redness * Headaches of a new type/pattern/severity * Lymph node tenderness * Frequent or recurring sore throat 3. CFS symptoms for ≥12 months 4. Participant completes daily self-report during the 4-week baseline period; 5. Able to attend UAB on all scheduled appointments Exclusion Criteria: 1. Blood draw contraindicated or otherwise not able to be performed 2. High-sensitivity c-reactive protein (HS-CRP) ≥3 mg/L 3. Erythrocyte sedimentation rate (ESR) \>60 mm/hr 4. Positive rheumatoid factor 5. Positive anti-nuclear antibody (ANA) 6. Levels of thyroid stimulating hormone or free thyroxine outside UAB lab reference values 7. Diagnosed rheumatological or auto-immune condition 8. Clotting disorder 9. Use of blood thinning medication 10. Oral temperature \>100˚F at baseline 11. Febrile illness or use of antibiotics in the 4 weeks before study commencement; 12. Planned surgery or procedures during the study period, or operated on in the 4 weeks before study commencement 13. Pregnant or planning on becoming pregnant within 6 months 14. Regular use of any anti-inflammatory medication (such as aspirin, ibuprofen, naproxen) 15. Known allergy or adverse effects following naltrexone or naloxone administration 16. Opioid use (self-reported or positive on urine test) 17. Significant psychological comorbidity that in the discretion of the investigator compromises study integrity and/or a baseline HADS depression subscale score of ≥16 18. Current litigation or worker's compensation claim 19. Current participation in another treatment trial 20. Vaccinated in the 4 weeks before study commencement (vaccination during the study period is allowed as long as the drug is administered at least 4 weeks prior to a study blood draw).