The World Health Organization Quality of Life (WHOQOL-100) instrument was developed to assess quality of life from a multi-dimensional perspective. A shorter 26-item version of the instrument was created called the WHOQOL-BREF, which is the focus of this study. Based on previous research, it is unclear if the WHOQOL-BREF instrument is appropriate for use with English-speaking, American college populations. The purpose of this study was to assess the reliability and construct validity of English-speaking, American College Students' responses to WHOQOL-BREF. One thousand seven hundred and seventy-three American college students from a southeastern university completed the WHOQOL-BREF in a confidential online format. Factor analyses were conducted and model fit was assessed using multiple fit indices. A Confirmatory Factor Analysis indicated that the prescribed four-factor model did not provide a good fit for the current data. An Exploratory Factor Analysis indicated a five-factor model was the best fit. However, the results of goodness-of-fit indices indicated the five-factor model was also a poor fit. This research showed inadequate construct validity through confirmatory factor analysis. Further validation studies of the instrument with English-speaking, American college students are recommended. (Contains 3 tables.)