PurposeThere is limited research on the work alienation of knowledge workers in management studies. This paper seeks to address this gap by exploring the extent and reasons for the alienation of knowledge workers.Design/methodology/approachIn the absence of a comprehensive framework for understanding the work alienation of knowledge workers, various factors such as structural elements of centralization and formalization, work characteristics of autonomy, variety, creativity, meaningfulness and self‐expressiveness, quality of work relationships and justice perceptions were examined as predictors of work alienation. Survey data were collected from six different organizations in the information technology sector (n=1,142) in India.FindingsAround 20 percent of the sample was found to be alienated from work. The strongest predictors of work alienation for knowledge workers were found to be lack of meaningful work, inability of work to allow for self‐expression, and poor quality work relationships.Research limitations/implicationsOrganizations employing knowledge workers cannot risk alienating them. The study indicates that one in every five knowledge workers is likely to be alienated. For organizations and practitioners this is a wake up call, pointing to the urgent need to try and understand the factors that are likely to cause alienation among knowledge workers and take adequate preventive steps to ensure an enthused workforce.Originality/valueResearch on alienation in present times has been somewhat limited. This is the first research of its kind across knowledge workers in the information technology industry that attempts to capture their work alienation and factors predicting it.