COVID-19 is a systemic disease. Since the beginning of the pandemic, there have been increasing reports of neuropsychiatric complications of the infection. The excessive inflammatory response during the infection induces changes in neurotransmission, which can result in nonspecific manifestations of affective and psychotic disorders, among other symptoms. We present descriptions of two cases involving previously untreated psychiatric patients, in whom the first-episode psychosis occurred immediately after SARS-CoV-2 infection. The commonality between both cases, besides the preceding SARS-CoV-2 infection, was the nonspecific and highly variable course of the psychotic disorder episode. This led to numerous diagnostic challenges and the necessity to change the diagnosis during treatment for both patients. In the case of a 58-year-old woman, persistent delusional disorders were initially diagnosed, followed by organic affective disorders. However, the evolution of symptoms ultimately led to the diagnosis of severe psychotic depression. In the case of a 68-year-old man, initially diagnosed psychotic depression turned out to be a first-episode of late-onset schizophrenia. Due to significant symptom exacerbation and evident treatment resistance, electroconvulsive therapy was implemented, resulting in complete symptomatic and functional remission. The first-episode psychosis post-COVID-19 is a newly emerging complication of infection, increasingly reported but still poorly defined and described in the literature. It appears to exhibit significant differences from previously encountered disease entities. The described cases underscore the ongoing need to consider a history of SARS-CoV-2 infection as a precipitating factor for first-episode psychoses, as it can impact both the course of the illness and diagnostic and therapeutic decisions.