Objectives Assessment of serum levels of IL-23 in PsA patients and its correlation with depression, anxiety, and disease activity. Methods Eighty psoriatic arthritis (PsA) patients and eighty healthy volunteers matched for age and gender were included in this observational case–control study. All participants suspected to detailed history, clinical assessment, PsA activity using Disease Activity Index for Psoriatic Arthritis (DAPSA) score, the severity and extent of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI), and ultrasonographic assessments of the entheses were examined according to the Madrid Sonographic Enthesitis Index (MASEI). Depression and anxiety were assessed by Hospital Anxiety and Depression Scale (HADS). Serum IL-23 was measured and correlated with disease activity, depression, and anxiety. Results There was no significant difference between patients and controls regarding demographic data. Thirty-six PsA patients (45%) had anxiety and 28 patients (35%) had depression, while in the control group, 16 persons (20%) had anxiety and 12 (15%) had depression, with significant differences between the 2 groups (p < 0.0001). There were significant differences in HADS anxiety and depression scores between patients and controls with significant positive correlations between HADS depression, anxiety scores and IL-23, DAPSA, PASI, and MASEI scores (p < 0.05). IL-23 was positively correlated with DAPSA, PASI, and HADS scores; we observed that interleukin 23, higher DAPSA, and PASI were independently associated with depression and anxiety. Conclusion Serum interleukin-23 levels were elevated in PsA patients and were found to be correlated with depression, anxiety, and disease activity. Key Points• Psoriatic arthritis is a multidimensional disorder with psychiatric drawbacks.• Interleukin-23 is a proinflammatory cytokines that was correlated with depression and anxiety in PsA patients.• Interleukin-23 was correlated with disease activity in PsA.• Depression and anxiety were positively correlated with disease activity in PsA.