(1) Background: The large global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overloaded the public health systems and reduced the regular healthcare activity, leading to a major health crisis. The main objective of this study was to carry out a comparative evaluation of the healthcare activities in the hospitals of Eastern Andalusia, Spain. (2) Methods: In this study, an observational, multicentered, and retrospective approach was adopted to compare the healthcare activities of the Poniente Hospital (PH) and the Alto Guadalquivir Health Agency (AGHA). Data was collected over a period of 24 months, i.e., from 1 January 2019 to 31 December 2020, and the variables evaluated were: patients seen in the hospital emergency service (HES), X-ray tests performed, patients cited in outpatient consultations, surgical interventions performed, and patients included in the waiting list. (3) Results: The analysis of the above-mentioned variables revealed a significant reduction in the number of patients registered in 2020 at HES as compared to that in 2019 for both PH (p = 0.002) and AGHA (p < 0.001). Moreover, the number of surgical interventions in 2020 was significantly reduced from that in 2019 for both PH (p = 0.001) and AGHA (p = 0.009). Moreover, for PH (p < 0.001), a significant reduction was observed in the waiting list admissions in 2020 compared to that in 2019; however, no significant difference in the waiting list admissions between the years 2020 and 2019 was observed for AGHA (p = 0.446). In 2020, the number of teleconsultations was significantly increased from that in 2019 for both PH (p < 0.001) and AGHA (p = 0.006). (4) Conclusion: The analysis carried out indicates that in 2020, compared to 2019, healthcare activity was significantly reduced in most of the parameters included in this study.