Background: Therapeutic plasma exchange is a procedure which removes plasma that contains circulating pathogenic substances, such as auto reactive antibodies, immune complexes, paraproteins, lipoproteins, inflammatory mediators like cytokines and return of the patient's blood components along with replacement fluid such as 5% albumin, fresh frozen plasma (FFP) or a combination of a crystalloid and colloid solution. Aim of the study: Assess nurses' performance regarding patients undergoing therapeutic plasma exchange. Research design: A descriptive exploratory design was utilized. Setting: The study was conducted at the therapeutic plasma exchange room in the combined dialysis unit affiliated to Ain Shams University Hospitals. Subjects: A convenience sample of all available nurses (no= 35) who are working in the previously mentioned setting. Tools: Two tools were used in the current study: Tool 1) self-administrated questionnaire and tool 2) observational checklist. Results: More than three quarters of the studied nurses had unsatisfactory level of total knowledge and had incompetent level of total practice regarding the patients undergoing therapeutic plasma exchange. There was a highly statistically significant relation between total nurses' education level, attendance of training courses for therapeutic plasma exchange and nurses` level of knowledge and practice. Conclusion: It can be concluded that the majority of studied nurses had poor nurses' performance (knowledge and practice) and there was positive correlation between total knowledge score and total practices score regarding care of patients undergoing therapeutic plasma exchange. Recommendations: Nursing educators and clinical facilitators must incorporate strategies using learning opportunities to raise awareness of nursing staff about topics of TPE` knowledge and practice. Ongoing and regular in-service training regarding basic procedures as: pre procedure, during procedure and post procedure of TPE.