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Background: Cytomegalovirus (CMV) pertains to the family of Herpes virus and is DNA double-stranded virus that affects around 70% of people worldwide. Purpose: The purpose of the current study is to determine how a learning package guidelines affected patients' knowledge, severity of symptoms, and quality of life with CMV colitis. Methods: A quasi experimental research model (pre-post test & follow up) has been utilized to conduct such study. A purposive sample of 60 adult subjects confirmed with cytomegalovirus colitis have been recruited in the current study. The following four data collection instruments were utilized: Instrument I: Interview assessment questionnaire composed of 2 parts; Part I: Patient's demographic characteristics data; Part II: Patient's knowledge questionnaire about CMV.Instrument II: Cytomegalovirus virus colitis - severity symptom scale. Instrument III: Cytomegalovirus virus colitis -QOL questionnaire. Instrument IV: L earning package and non-pharmacological regimen. Results: Post implementation of learning package enhanced patients' knowledge of CMV colitis, with significant variations pre/post and pre/follow-up scores (P<0.001*). Furthermore, there were very statistically significant differences in mean scores of symptom severity for CMV colitis patients pre, post, and follow -up learning package. Post and follow-up learning package guidelines implementation resulted in significantly higher mean scores on CMV colitis-QOL subscales compared to preimplementation (p < 0.001). Conclusion: Patients with CMV colitis have noticed a decrease in the severity of their symptoms and an improvement in their quality of life after applying the learning package is implemented. Recommendations:Patients' awareness of the CMV colitis symptoms and its related factors should be raised which support its development. [ABSTRACT FROM AUTHOR]