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A wide spectrum of neurological symptoms (NS) has been described in patients with COVID‐19. We examined the plasma levels of neuron‐specific enolase (NSE) and neurofilament light chain (NFL) together, as neuronal damage markers, and their relationships with clinical severity in patients with NS at acute COVID‐19. A total of 20 healthy controls and 59 patients with confirmed COVID‐19 were enrolled in this pilot prospective study. Serum NSE and NFL levels were measured by using the enzyme‐linked immunoassay method from serum samples. Serum NSE levels were found to be significantly higher in the severe group than in the nonsevere group (p = 0.034). However, serum NFL levels were similar between the control and disease groups (p > 0.05). For the mild group, serum NFL levels were significantly higher in patients with the sampling time ≥5 days than in those with the sampling time <5 days (p = 0.019). However, no significant results for NSE and NFL were obtained in patients with either single or multiple NS across the groups (p > 0.05). Increased serum NSE levels were associated with disease severity regardless of accompanied NS in patients with acute COVID‐19 infection. However, serum NFL levels may have a role at the subacute phase of COVID‐19.

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