Background: Cancer cells may metabolize glutamine to fulfill their metabolic needs. In prostate cancer it has been shown that androgen receptor signaling promotes glutamine metabolism by increasing the expression of the glutamine transporters, and that stromal glutamine may promote tumor growth. Methods: We retrospectively tested glutamine levels in frozen plasma samples from mCRPC patients treated with taxanes, which were included in a prospective biomarker study in our institution. Glutamine levels were determined by a bioluminescent assay. Optimal cut-offs for glutamine levels were assessed using maximally selected log-rank statistics to determine low and high level groups. Pre-treatment glutamine level was correlated with taxanes response and clinical outcome. Independent association with survival was evaluated by multivariate Cox modeling. Results: Seventy eight mCRPC patients treated with taxanes were included. Median age was 70.3 (55.8-83.5) years and median follow-up was 13.1 (0.2-53.9) months. Glutamine was tested in 88 plasma samples: 69 from pre-docetaxel and 19 pre-cabazitaxel treatment (10 patients had both samples). High glutamine levels significantly correlated with worst PSA-progression-free survival (PFS) (median 2.8 vs 4.7 months, hazard ratio [HR] 1.8, 95%CI 1.1-2.7, P= 0.012) and overall survival (OS) (median 12.4 vs 20.4, HR 2, 95%CI 1.2-3.3, P= 0.006). In a multivariate analysis, high plasma glutamine levels were independently associated with shorter PSA-PFS (HR 2.3, 95%CI 1.4-3.7, P< 0.001) and OS (HR 2.2, 95%CI 1.3-3.7, P= 0.003). Patients with high glutamine levels were more likely to present PSA progression to taxanes than those with low levels (odds ratio [OR] 3, 95%CI 1.2-7.7, P= 0.016). Moreover, samples from patients treated with abiraterone or enzalutamide before taxanes (51 samples from 43 patients) had significantly higher glutamine levels (T-test, P= 0.014) than those without these prior therapies. Conclusions: Glutamine can be detected in plasma of mCRPC patients and higher levels are associated with adverse clinical outcome, supporting the relevance of metabolism in prostate cancer progression.