Individuals diagnosed with COVID-19 are at a higher risk of arterial and venous thrombosis, mostly pulmonary microvascular thrombosis, which may significantly impair treatment and result in morbidity. This is a systematic review and meta-analysis of research papers that aim to evaluate the risk of bleeding and thrombosis among patients treated with low molecular weight heparin or fondaparinux (LMWH/F). Additionally, we measured the overall death events. This study was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A search was conducted in the Clinicaltrials.gov, PubMed, Scopus, and Web of Science databases to identify observational cohort studies and randomized-controlled clinical trials (RCTs) that compared LMWH/F in proven COVID- 19 patients. A total of 220 people from two studies were included. Patients who were treated with fondaparinux had a lower risk of developing venous thromboembolism (VTE) (odds ratio (OR) 0.39; 95% confidence interval (CI) (0.14, 1.096); p = 0.168); pulmonary embolism (OR 0.169, 95% CI (0.021, 1.356), p = 0.094); and deep vein thrombosis compared to patients who received LMWH therapy. The data show a lower mortality rate in the LMWH groups (OR 1.135, 95% CI (0.463, 2.785), p = 0.781) and a lower frequency of bleeding (OR 1.657, 95% CI (0.456, 5.908), p = 0.436). Both drugs have shown anti-thrombotic properties in COVID-19 patients. Fondaparinux was somewhat more effective in reducing thrombosis episodes. This research demonstrates the safe use of LMWH for VTE prophylaxis in hospitalized COVID-19 patients based on bleeding and mortality outcomes.