COVID-19 significantly altered our routine, lifestyle, and stress level across the globe. This study investigated the psychological impact of COVID-19 on healthcare workers in China Xi'an Center hospital. A modified online questionnaire of Psychological Status and the General Health Questionnaire (GHQ-12) was provided to 1,967 healthcare workers during the COVID-19 pandemic. Participation was voluntary, and the responses were anonymous. The survey lasted for 2 weeks, and the GHQ-12 was completed every other day. The data were collected automatically and electronically and then statistically analyzed. The 431 (21.9%) responders included 214 nurses (49.7%), 146 clinicians (33.9%), 29 pharmacists (6.7%), 15 medical technicians (3.5%), 17 administrative staff (3.9%), and 10 other departments (2.3%). Of these, 46.2% had 10 years of work experiences or more and 78.2% were married. Work experience increased emotional stress as 23% of participants with 10 years or more of experience exhibited higher stress compared to those with fewer than 3 years of work experience (7.5%). Moreover, 33.3% of participants who worked in or were exposed to the affected areas of the pandemic experienced psychological stress. Overall, this study identified four factors that were significantly associated with psychological stress: (a) work experience (OR 2.99; 95% CI: 1.06 to 8.41); (b) change in job position (OR 1.99; 95% CI: 1.10 to 3.59); (c) change in lifestyle (OR 4.06; 95% CI: 1.81 to 9.10); and (d) need for psychological counseling (OR 3.07; 95% CI: 1.62 to 5.82). The COVID-19 pandemic has increased psychological stress among healthcare workers with 10 years or more work experiences and who recently experienced a career position change.