An out-of-season opportunistic H3N2 type A influenza epidemic occurred in the state of Rio de Janeiro, Brazil during October-November 2021, in between the Delta and Omicron SARS CoV-2 surges. We assessed the contribution of climate change and influenza immunization coverage in this unique, little publicized phenomenon. State weather patterns during the influenza epidemic were significantly different from the five preceding years, matching typical winter temperatures. There was also a mismatch between influenza vaccine strains used in the winter of 2021 (trivalent vaccine with two type A strains (Victoria/2570/2019 H1N1, Hong Kong/2671/2019 H3N2) and one type B strain (Washington/02/2019, wild-type) and the circulating influenza strain responsible for the epidemic (H3N2 Darwin type A influenza strain). In addition, in 2021 there was poor influenza vaccine coverage with only 56% of adults immunized. Amid the COVID-19 pandemic, we should be prepared for out-of-season outbreaks of other respiratory viruses in periods of COVID-19 remission. The availability of year-round influenza vaccines could help avoid unnecessary morbidity and mortality given that antibodies rapidly wane. Moreover, this would enable unimmunized individuals to have additional opportunity to vaccinate during out of season outbreaks.