The coronavirus diseases 2019 (COVID-19) is a worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). This research is therefore aimed at using experimental design to derive a model for the spread of COVID-19 in West Africa. In effect, 3<sup>2</sup> factorial design with mixed factors was used to design the data layout with country as the random factor and status of COVID-19 patient as the fixed factor. Under country, Nigeria, Senegal and Ghana were randomly selected as the three levels from the seventeen West African countries while under status of COVID-19 patient, recovery, death and active cases were the three fixed levels used. The data for the study were collected based on the monthly recorded number of the various COVID-19 cases (i.e. recovery cases, death cases and active cases out of the total confirmed cases) for the period from February to September, 2020. The data were retrieved from the reports on COVID-19 given by the respective country’s health authorities and published on their various websites. In effect, a mixed effect model was derived through formulation processes for the prediction of the various COVID-19 cases across West Africa. Also, different residual analyses were conducted for the model adequacy checking and it proved that the model was adequate in the estimation of the various COVID-19 cases in the West African Sub-region. This therefore makes it the first time experimental design and analysis has successfully been used for a study of this nature on the spread of COVID-19 in West Africa.