Cryptococcal meningitis (CM) is a common opportunistic infection with a high mortality rate in human immunodeficiency virus (HIV)-infected patients. It is unclear whether mannitol could be used to manage neurological symptoms in HIV-associated CM. Here, we retrospectively analyzed the clinical data of 33 patients with HIV-associated symptomatic CM at our hospital where mannitol was used to relieve neurologic symptoms. With the empirical mannitol therapy, patients had a median of 2 episodes (range, 1-6 episodes) of headaches the day at the starting of anti-cryptococcal therapy. The median score of pain intensity assessed by numerical rating scales was 7-point (range, 4-8 points). After the administration of mannitol, the score of pain intensity was reduced to 3-point or less. Three weeks after anti-cryptococcal therapy, 75.8% (25/33) of the patients did not report headaches. During the initial 3 weeks of anti-cryptococcal therapy, 13 patients had a total of 42 episodes of seizures. 97.6% (41/42) of the episodes of seizures were controlled after the administration of mannitol. Overall, 87.9% (29/33) of the patients survived more than 10 weeks without the need of therapeutic cerebrospinal fluid drainage. Mannitol was used for median of 26 days (range, 1-85 days) in these 29 patients. One patient had permanent vision loss. This study indicates that mannitol may possibly relieve neurologic symptoms in HIV-associated CM. It is worth re-revaluating the role of mannitol administration as a symptom control strategy in mild cases of HIV-associated CM.