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A 34-year-old HIV-positive man with a history of chronic substance abuse was admitted with dual infection of Streptococcus pneumoniae and Listeria monocytogenes. Combined bacteraemia with S. pneumoniae and L. monocytogenes is very rare. To the best of our knowledge, this is the first such case documented at our institution and in South Africa. Ampicillin should be added to antibiotic regimens to improve patient outcome if L. monocytogenes infection is suspected. Co-infections that occur with L. monocytogenes may have conflicting antibiotic treatment options. This case report emphasises the need for a good relationship between the local microbiology pathologist and physician to select appropriate antibiotic treatment before definitive results are available.