Background A recent factor analysis of Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) data in a sample of schizophrenia-spectrum patients described a three factor model representing processing speed, attention/working memory, and learning; the social cognition measure was excluded from the analysis. The current analyses sought to replicate a three factor structure of the MCCB in a larger, more diagnostically diverse sample of participants. Methods Confirmatory factor analyses were performed to evaluate the factor structure of the MCCB in 300 outpatients with severe mental illness (54.3% schizophrenia-spectrum diagnoses) who were participants in three studies of cognitive remediation. Exploratory analyses were conducted to evaluate the concurrent prediction of symptoms from MCCB factor scores. Results The three factor structure of the MCCB demonstrated stronger model fit (χ2 =14.53, p =0.75, SRMR=0.02, RMSEA=0.0, CFI=1.00, NNFI=1.01) than the unifactoral structure. Poorer cognitive performance across all three MCCB factors was significantly correlated with more severe overall and disorganization symptoms from the PANSS and BPRS, and less severe affective symptoms (e.g., depression, anxiety) in the overall sample. Conclusions A three factor structure of the MCCB—composed of processing speed, attention/working memory, and learning—was replicated in a heterogeneous sample of persons with severe mental illness. Cognitive performance on the MCCB factors is associated with clinical symptoms.