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Wearing face masks has resulted in verbal communication being more challenging during the COVID-19 pandemic. This study aimed to investigate the effect of face masks on the speech comprehensibility of Persian nurses in healthcare settings. Twenty female nurses from the governmental hospitals randomly participated in an experiment on seven typical commercial face masks at two background noise levels. Nurses' speech intelligibility from a human talker when wearing each face mask was determined based on the speech discrimination score. The vocal effort of nurses wearing each face mask was determined based on the Borg CR10 scale. Based on the linear mixed model, the speech intelligibility of nurses from a human speaker wearing surgical masks, N95 masks, and a shield with face masks were approximately 10%, 20%, and 40–50% lower, respectively, than no-mask conditions ( p < 0.01). The background noise decreased the speech intelligibility of nurses by approximately 22% ( p < 0.01). The use of a face shield further decreased speech intelligibility up to 30% compared to using a face mask alone ( p < 0.01). The vocal efforts of nurses when wearing surgical masks were not significant compared with the baseline vocal efforts ( p > 0.05); however, vocal efforts of nurses when wearing N95 and N99 respirators were at an unacceptable level. The face masks had no considerable effect on the speech spectrum below 2.5 kHz; however, they reduced high frequencies by different values. Wearing face masks has a considerable impact on the verbal communication of nurses in Persian. The level of background noise in the healthcare setting can aggravate the effect sizes of face masks on speech comprehensibility.