Abstract Background The post-COVID-19 condition is a major modern challenge in medicine and has a high global impact on the health of the population. Objective To determine the main neurological and neuropsychiatric manifestations after acute COVID-19 infection in South American countries. Methods This is a systematic review study, registered on the PROSPERO platform following the PRISMA model. 4131 articles were found with the search strategies used. Neurological and neuropsychiatric manifestations were investigated in individuals three months or more after acute COVID-19 infection, and older than 18 years, including studies conducted in South American countries published between 2020 and 2022. Results Six studies (four from Brazil and two from Ecuador) were analyzed. Regarding the type of study: three were cohorts, two were case reports, and one was cross-sectional. The main outcomes found were new pain (65.5%) and new chronic pain (19.6%), new headache (39.1%), daily chronic headache (13%), paresthesia (62%), in addition to neuropsychiatric diseases, such as generalized anxiety disorder (15.1%), post-traumatic stress syndrome (13.4%), depression and anxiety (13.5%), suicidal ideation (10.1%), and several cognitive disorders. Conclusion Neurological and neuropsychiatric manifestations related to depression and anxiety, and cognition disorders are reported during the post-COVID-19 condition in South America. Symptoms associated with chronic pain appear to be associated with the condition. More studies on post-COVID-19 conditions are needed in the South America region.