Colorectal cancer and its treatment may cause adverse effects to the social function, including work and productive life, relationship with the family, partners and friends, and other interests and social activities, the disease and treatment impact to patients' well-being and functional results is a topic of growing interest for the colorectal cancer researches. Although improvements in treatment regimens have beneficially impacted the prognosis of colorectal cancer, several quality of life issues result from potential side effects of such aggressive treatment. This study aimed to assess the effect of chemotherapy on quality of life for colorectal cancer patients before the beginning and 21 days after the first session of chemotherapy. The study was carried out in outpatient of the Cancer Institute. The sample consists of 80 patients diagnosed as colorectal cancer, postoperatively and undergoing chemotherapy. The European Organization for Research and Treatment of Cancer-Quality of life Core-30 (EORTC QLQ-C30) questionnaire was used to assess patient's quality of life. Data were collected over a period of seven months started from September 2009 to March 2010. The results revealed that all symptoms dimensions except fatigue, and functional dimensions related to physical, role, and cognitive functioning as well as overall functioning was significantly decreased post the chemotherapeutic session. Conclusion and recommendation explained that; for the improvement of quality of life, patients with colorectal cancer undergoing chemotherapy should be included in program to help them find out adopt, and deal with function and symptoms complication of chemotherapy. [Omibrahem A. Elsaie, Hend M. Elazazy and Seham A. Abdelhaie. The Effect of Chemotherapy on Quality Of Life of Colorectal Cancer Patients before and 21 Days after the First Chemotherapeutic Sessions. Life Sci J 2012;9(4):3304-3314]. (ISSN: 1097-8135). http://www.lifesciencesite.com. 489