The isolation of Zika virus (ZIKV) from serum of suspected human cases for diagnostic purposes can be challenging due to infrastructure constraints of laboratory testing technology. Therefore, as an alternative method, the objective of this study was to evaluate a random sample of oropharyngeal swabs for the diagnosis of ZIKV infection among patients with symptoms of arboviral and respiratory illness. The results revealed that ZIKV RNA could be detected by a reverse transcriptase polymerase chain reaction (RT-PCR) assay and isolated from oropharyngeal swabs from five of 38 samples, but serum samples from the same patients were negative for ZIKV by a variety of laboratory diagnostic approaches including RT-PCR and viral isolation followed by immunofluorescence assays. The findings suggested that the molecular detection and isolation of ZIKV in oropharyngeal swab warrants further study for consideration as an improved diagnostic procedure.