What are fertility staff experiences of managing COVID-19-related uncertainty after fertility clinics re-opened? Staff identified many COVID-19-related uncertainty sources, the main being the COVID-19 health threat, to which most clinics and staff responded effectively by implementing safety protocols and building strong collaborative environments that facilitated the acquisition and application of information to guide organizational responses during a rapidly changing situation, but with costs for staff and patients. COVID-19 created significant disruption in fertility care delivery, including temporary clinic closure and treatment delay. Patients experienced significant distress, including concerns regarding the impact of COVID-19 and its vaccine on fertility and pregnancy. Multiple studies show that COVID-19-related uncertainty is a major threat and burden for healthcare staff, but this has not been investigated in reproductive medicine. A cross-sectional, online mixed-method bilingual (English, Spanish) survey (active 25 January-23 May 2021) was distributed to fertility staff across the UK, Latin America, and Africa. Eligibility criteria were being a healthcare worker at a fertility clinic that had re-opened since its COVID-19-related closure, 18 years of age or older and ability to respond in English or Spanish. The survey was created in English, translated to Spanish, made available using Qualtrics, and consisted of four parts: (i) background and physical and mental wellbeing, (ii) open-ended questions regarding COVID-19 uncertainty, (iii) appraisal items regarding perceptions and impact of uncertainty, and (iv) changes in the workplace. The British Fertility Society and the African Network and Registry of Assisted Reproduction circulated the survey across the UK and Africa via email hyperlinks and social media platforms. The Argentinian Society of Reproductive Medicine and the Latin American Network of Assisted Reproduction distributed the survey across Latin America in the same manner. Thematic analysis was performed on responses from open-ended question to produce basic codes. Deductive coding grouped sub-themes across questions into themes related to the theory of uncertainty management. Descriptive statistics and repeated measures analysis of variance were used on the quantitative data. In total, 382 staff consented to the survey, 107 did not complete (28% attrition), and 275 completed. Sixty-three percent were women, 69% were physicians, and 79% worked at private clinics. Thematic analysis produced 727 codes, organized in 92 sub-themes, and abstracted into 18 themes and one meta-theme reflecting that uncertainty is stressful but manageable. The types of uncertainties related to the threat of COVID-19 (20.6%), unpredictability of the future (19.5%), failure of communication (11.4%), and change in the workplace (8.4%). Staff appraisals of negative and positive impact of uncertainty were significantly lower (P < 0.001) than appraisals of stress, controllability, and having what it takes to cope with uncertainty. To process uncertainty, clinics focused on information dissemination (30.8%) and building a collaborative work environment (5.8%), while staff employed proactive coping (41.8%) and emotional and cognitive processing (9.6%). Main organizational responses consisted on work restructuring (41.3%, e.g. safety protocols), adapting to adversity (9.5%, e.g. supplies, preparation), and welfare support (13.8%), though staff perceived lack of support (17.5%). Negative consequences of uncertainty were worse self- and patient welfare (12.1%) and worse communication due to virtual medicine and use of mask (9.6%). Positive consequences were work improvements (8.3%), organizational adaptation (8.3%), improved relationships (5.6%), and individual adaptation (3.2%). Ninety-two percent of participants thought changes experienced in the workplace due to COVID-19 were negative, 9.1% nor negative nor positive, and 14.9% positive. Most staff thought that their physical (92.4%) and mental health (89.5%) were good to excellent. Participants were self-selected, and most were physicians and embryologists working at private clinics based in Latin America. The study did not account for how variability in national and regional COVID-19 policy shaped staff experiences of uncertainty. To address COVID-19 uncertainty, clinics need to promote collaborative (clinic, staff, patients) processing of uncertainty, clear team coordination and communication, organizational flexibility, and provision of support to staff and patients, with an emphasis on cognitive coping to decrease threat of and increase tolerance to uncertainty. Uncertainty management interventions bespoke to fertility care that integrate these components may increase clinics resilience to COVID-19-related and other types of uncertainty. Cardiff University funded this research. S.G. reports consultancy fees from Ferring Pharmaceuticals A/S, speaker fees from Access Fertility, SONA-Pharm LLC, Meridiano Congress International, and Gedeon Richter, and grants from Merck Serono Ltd. F.Z.-H. reports speaker fees from Ferring Pharmaceuticals A/S and that he is a chair of the Latin American Registry of ART, Committee of Ethic and Public Policies, and Chilean Society of Obstetrics and Gynecology and a vice chair of the International Committee for monitoring ART. K.A., N.C., G.B., and J.B. report no conflict in relation to this work. N/A.