Whether depressed patients with evidence of inflammation are more appropriate candidates for immunotherapies is being tested in several clinical trials, which are selecting patients based on elevated C-reactive protein (CRP) and inflammation-related symptoms. However, studies of the clinical and phenotypic profile of depressed patients with elevated CRP are relatively scarce. We have investigated detailed clinical characteristics of 84 depressed patients, grouped as those with (CRP≥3 mg/L) and without (CRP<3 mg/L) inflammation. All patients met the International Classification of Diseases 10th Revision criteria for current depressive episode and had somatic symptoms of depression. We report that depressed patients with inflammation are more likely to be older (P=0.04), have higher body mass index (P<0.01), and be on non-selective serotonin reuptake inhibitor anti-depressants (P=0.04). After adjusting for potential confounders, the inflammation group had higher depression severity (adjusted mean difference, 8.82; 95% CI, 3.91-13.72), somatic symptoms (adjusted mean difference, 3.25; 95% CI, 1.58-4.92), state anxiety (adjusted mean difference, 9.25; 95% CI, 3.82-14.67), perceived stress (adjusted mean difference, 4.58; 95% CI, 1.98-7.18), and fatigue (adjusted mean difference, 9.71; 95% CI, 3.09-6.33), but not anhedonia. The inflamed group also had poorer quality of life (adjusted mean difference, -0.18; 95% CI, -0.32-0.05). At individual depressive symptom level, the inflammation group had increased guilty feelings (adjusted odds ratio [OR], 7.28; 95% CI, 2.09-31.17), pessimism (adjusted OR, 5.38; 95% CI, 1.53-22.73), concentration difficulties (adjusted OR, 4.56; 95% CI, 1.32-19.02), and indecisiveness (adjusted OR, 4.21; 95% CI, 1.15-18.54). Our findings highlight the clinical features associated with inflammation in depressed patients with somatic symptoms, including poor quality of life, supporting the need for intervention targeting this group. These results could also aid patient and outcome selection in future clinical trials testing immunotherapies in depression. Replication of these findings in larger samples is required.