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Background:  Health related quality of life (HRQOL) has emerged as an important outcome of health care.  Debate continues about the dimensions of HRQOL in relation to their relative importance, the strength of their influence and their dynamic nature.  Wilson and Cleary's HRQOL conceptual model suggests that functional health status mediates the relationship between symptom status and QOL.  Therefore the aim of this study was to examine the effect of functional status on the relationship between symptom status and QOL.  Methods:  There were 956 HIV+ patients in this analysis.  Analysis to test the mediation model was done using Structural Equation Modeling in Mplus.  The measurement of symptom status was based on the "Sign and Symptom Checklist for Persons with HIV Disease", functional status was based on the "Health Assessment Questionnaire-Disability Index", and the QOL measurement was based on work from the Medical Outcomes Study.  Symptom status has been theorized to have both a direct and an indirect effect on QOL.  Indirectly it is hypothesized that symptom status influence on QOL is mediated by functional status.  The mediation model that was tested hypothesizes that functional status mediates the relationship between symptom status and QOL. Results:  The hypothesized negative relationship between symptom status and QOL was supported (ß = -2.028, S. E. + 0.100).  The negative estimate indicates that patients with more symptoms reported a lower perceived QOL.  There was a statistically significant indirect or mediation effect in that the number of reported symptoms influenced the individual's functional status which then influenced their perceived QOL.  Conclusions:  The management of symptoms is important for the HRQOL of patients.  In clinical practice it is important to understand what processes influence this relationship.  This analysis showed an individual's functional status influences the relationship between symptom status and QOL.  Clinical implications of this relationship will be discussed.