Background Novel coronavirus (SARS-CoV-2) infects human lung tissue cells through angiotensin-converting enzyme-2 (ACE2), and the body sodium is an important factor for regulating the expression of ACE2. Through a systematic review, meta-analysis and retrospective cohort study, we found that the low blood sodium population may significantly increase the risk and severity of SARS-CoV-2 infection. Methods We extracted the data of serum sodium concentrations of patients with COVID-19 on admission from the articles published between Jan 1 and April 28, 2020, and analyzed the relationship between the serum sodium concentrations and the illness severity of patients. Then we used a cohort of 244 patients with COVID-19 for a retrospective analysis. Results We identified 36 studies, one of which comprised 2736 patients.The mean serum sodium concentration in patients with COVID-19 was 138.6 mmol/L, which was much lower than the median level in population (142.0). The mean serum sodium concentration in severe/critical patients (137.0) was significantly lower than those in mild and moderate patients (140.8 and 138.7, respectively). Such findings were confirmed in a retrospective cohort study, of which the mean serum sodium concentration in all patients was 137.5 mmol/L, and the significant differences were found between the mild (139.2) and moderate (137.2) patients, and the mild and severe/critical (136.6) patients. Interestingly, such changes were not obvious in the serum chlorine and potassium concentrations. Conclusions The low sodium state of patients with COVID-19 may not be the consequence of virus infection, but could be a physiological state possibly caused by living habits such as low salt diet and during aging process, which may result in ACE2 overexpression, and increase the risk and severity of COVID-19. These findings may provide a new idea for the prevention and treatment of COVID-19.