Background: The COVID-19 pandemic poses psychosocial challenges to the oncology workforce. We postulate that these impacts may affect the entire patient-facing workforce. Whether distress is different in varying settings (metro vs regional hospitals) is unknown. Methods: Cancer Care staff were approached via all-staff email for a weekly online survey administered at two hospital sites, Royal Brisbane and Women’s Hospital (RBWH) (metro) and Sunshine Coast Hospital and Health System (SCHHS) (regional). Surveys included Likert-scale items exploring perceptions of departmental preparation, COVID-19 related query burden and staff well-being, and distress thermometer derived from NCCN. Mean and 95% confidence interval were calculated, with non-parametric t-tests adjusted for multiple comparisons (Holm-Sidak); significance was deemed p < 0.05. Results: 117 participants at RBWH and 59 at SCHHS consented. The survey opened April 3, 2020. Data is presented for the initial 6 weeks (COVID-19 preparation phase). Highest survey response was noted in week 1 (87%) and lowest at week 6 (36%). 65% unique responses were from RBWH. 60% participants worked in an outpatient setting, while 37% had inpatient care role. The remainder worked in either community-based or mixed settings. Significant heterogeneity was detected between sites (RBWH vs SCHHS) for some occupational roles: RBWH had more representation of administrative (19% vs 8%, p < 0.001) and ancillary staff (2% vs 0%, p = 0.005) but SCHHS had more allied health (28% vs 17%, p = 0.005). Nursing and medical staff proportions at SCHHS and RBWH were similar (50% vs 45%, and 14% vs 18% respectively). Higher levels of distress were noted early; mean (95% CI) distress thermometer result (0-10) during week 1 was 4.7 (4.3-5.2) at RBWH and 4.9 (4.2-5.5) at SCHHS. Mean distress scores significantly reduced over time: correlative scores during week 6 were 3.2 (2.3-4.1) at RBWH and 2.5 (1.6-3.4) at SCHHS. Distress levels comparing RBWH with SCHHS were similar (p = 0.22-0.76). No significant difference was noted in staff perception of self-support comparing RBWH with SCHHS, and over 80% responders felt well-supported at work most, or all of the time. Concurrently, participants perceived that the Cancer Care department of their site was either “well” or “very well” prepared for COVID-19 over 85% of the time, with no difference between sites. Conclusions: High perceptions of support and preparedness were evident, with no regional difference. Distress scores reduced over time during the COVID-19 preparation phase, in the context of low COVID-19 rates.