Background: COVID-19 caused restrictions and re-allocation of medical resources among all healthcare services. During the peak of the pandemic, several unrelated-yet critical-conditions had silently taken their toll. Infective endocarditis (IE), owing to its non-specific clinical presentation, may have been largely mislabeled as COVID-19 in a number of cases. Results: This retrospective observational study reviewed all IE presentations at an IE unit in a university hospital during the peak of COVID-19. Patient characteristics, courses, and outcomes were compared with historical controls from our IE database published before the COVID era. We identified 30 IE cases [Group A] during the COVID-19 peak in our region (June 2021 to June 2022), with a 25% decrease compared to the usual annual rate. This is in contrast to the expected surge during the pandemic. Compared with group B (398 published IE cases from our database), group A had significantly longer symptoms-to-presentation intervals (60 [31-92] vs. 28 [14-72] days, p = 0.01). Male sex dominated both groups, but group A had significantly less pre-existing structural heart disease. Despite the more liberal use of empirical antibiotics in the COVID-era, group-A had lower rates of culture-negative IE. Compared to group B, group A demonstrated a better response to medical therapy, fewer arterial embolizations, fewer indications for surgery, and fewer overall complications, except for increased acute kidney injury. This can be explained by the abundant use of non-steroidal anti-inflammatory drugs. The data analysis strongly suggests that there might have been a natural selection or selection bias of IE patients with favorable profiles to survive the pandemic to the appropriate diagnosis. Conclusions: The diagnosis of IE and commencing the appropriate workup were significantly undermined during the COVID-19 pandemic. The inexplicable decline in IE referral rate and the favorable outcomes witnessed during the pandemic strongly suggest a referral bias and natural selection of those who survived the pandemic to the appropriate IE diagnosis.