Background: The purposes of this study were to examine the impact of chemotherapy treatment on Jordanian cancer patients’ fatigue and to correlate their fatigue with selected sociodemographic variables at the beginning of treatment and after four weeks of treatment. Methods: This was a single group quasi-experimental correlational design study that enrolled 43 patients diagnosed with cancer who required chemotherapy treatment. Fatigue was measured according to the Piper Fatigue Scale (PFS) before starting chemotherapy treatment and after four weeks of receiving the first dose of chemotherapy. Data were collected over a period of four weeks and analyzed with descriptive statistics, the paired-sample t-test, and Pearson product-moment correlation.Results: The study included 17 (39.5%) males and 26 (60.5%) females with a mean age of 45.98 years. Most (n=17) were diagnosed with breast cancer. Obesity was present in about 64.4% of patients. The majority (46%) received an anthracycline-based regimen. There were statistically significant differences between respondents’ total mean scores of fatigue pre-treatment and four weeks following chemotherapy treatment (t= -2.31, df=42, P<0.05). In addition, significant differences were found in the scores for behavioral, affective, sensory, and cognitive dimensions subscales (t= -2.24, -2.19, - 2.4, -2.4, df=42, P<0.05) between pre-treatment and four weeks after receiving the first dose of chemotherapy treatment. We observed a significant negative relationship between fatigue scores and hemoglobin levels (r= -0.04, P<0.01).Conclusion: Cancer-related fatigue is common among cancer patients who received chemotherapy and result in substantial adverse physical, behavioral, cognitive and affective consequences for patient. Given the impact of fatigue, treatment options should be routinely considered in the care of patients with cancer.