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Introduction: Surgery is a very stressful situation for patients. In addition to physical variables, psychological components also affect the patients who are ready for surgery. This study aimed to investigate the relationship of psychological factors with immunological and physiological factors regarding the moderating role of personality trait D in patients ready for surgery at Imam Khomeini Hospital, Ilam, Iran.   Materials & Methods: The present study was conducted based on an analytical and correlational design. The population of this study included the patients who were ready to undergo surgery at Imam Khomeini Hospital, Ilam, Iran. In total, 60 people (30 females and 30 males) were selected using the available sampling method. The data were collected using Perceived stress questionnaire, Spielberger anxiety questionnaire, personality type D questionnaire (DS-14), and blood samples of the patients to measure the blood factors. The data were analyzed in SPSS software (version 21) using descriptive and inferential statistics.   Findings: The results showed a significant relationship of psychological variables (stress, anxiety, personality trait D) with immunological (cortisol) and physiological (blood factors) variables (P<0.01). The results of regression analysis also showed that psychological variables (stress and anxiety) are able to predict the immunological and physiological states of the patients who are ready for surgery. It is worth mentioning that personality trait D also plays a significant role in this regard.   Discussion & Conclusions: The results showed that the immune disorders during surgery created by psychological variables can cause biological changes in terms of health risk. Given the effect of psychological variables on the immune system, it is recommended to evaluate people with personality type D since this personality type can have effects on blood factors before and after surgery which can be an appropriate guideline for psychological interventions.