This study aimed to examine the association between workplace ostracism and nurses’ deviant work behaviors, highlighting the mediating roles of emotional exhaustion and defensive silence in this relationship. A descriptive correlational design was used to describe and examine relationships among these variables in a governmental hospital (Al-Ahrar Teaching Hospitals) in Egypt. Four standardized scales were used to assess workplace ostracism, deviant work behaviors, emotional exhaustion, and defensive silence among nurses; 257 nurses were surveyed randomly. AMOS structural equation modeling (SEM) was used to examine the hypothetical model of the study. Workplace ostracism had a significant direct effect on emotional exhaustion (β = 0.57, p < 0.001), defensive silence (β = 0.47, p < 0.001), and deviant work behavior among nurses (β = 0.41, p < 0.001). The indirect effect of workplace ostracism on nurses’ deviant work behavior, mediated by emotional exhaustion (β = 0.627, p = 0.001). Correspondingly, the indirect effect of workplace ostracism on nurses’ deviant work behavior is mediated by defensive silence (β = 0.033, p = 0.041). Also, the overall indirect effect of workplace ostracism on nurses’ deviant work behavior is mediated serially by emotional exhaustion and defensive silence (β = 0.660, p = 0.001).