Pentoxifylline (PTX) affects most blood components and the blood vessels, potentially modulating various conditions. Due to its impact on markers linked to COVID-19 severity, research has explored PTX for acute COVID-19. Following the widespread administration of COVID-19 vaccinations, there has been a notable and consistently growing increase in research focusing on long COVID. Consequently, our examination of relevant acute COVID-19 data shall additionally be contextualized into long COVID research. Various Databases were searched until July 2024 for all primary clinical studies on Pentoxifylline (PTX) in COVID-19. Studies were on acute infection with SARS-CoV-2 where PTX was an adjuvant to standard therapy for ethical and practical reasons under the circumstance. PTX generally reduced hospitalization duration and improved some inflammatory markers, but its impact on mortality was inconsistent. Adverse events were minimal. Meta-analysis revealed a significant reduction in hospitalization duration. This systematic review and meta-analysis suggest that adding pentoxifylline (PTX) to standard COVID-19 therapy may significantly reduce hospitalization duration and improve some inflammatory markers. However, its impact on mortality rates is inconclusive. Adverse events are minimal. PTX can be favorable as an add-on in managing acute COVID-19 and could reduce the risk of long COVID, as well as assist in managing many of its most common symptoms.