Evidence suggests that diet can play a role in modulating systemic inflammation. This study aims to examine the relationship between fatty acids (FAs) (self-reported dietary intake and red blood cell (RBC) membrane fatty acid concentrations), three diet quality scores, and the plasma concentrations of inflammatory markers (interleukin-6, IL-6; tumour necrosis factor alpha, TNF-α; and C-reactive protein, CRP) in a group of Australian adults (n= 92). Data were collected on their demographic characteristics, health status, supplement intake, dietary intake, RBC-FAs and plasma inflammatory markers over a nine-month period. Mixed-effects models were used to determine the relationship between RBC-FAs, dietary intake of FAs, diet quality scores and inflammatory markers to determine which variable most strongly predicted systemic inflammation. A significant association was identified between dietary saturated fat intake and TNF-α (β = 0.01,p< 0.05). An association was also identified between RBC membrane saturated fatty acids (SFA) and CRP (β = 0.55,p< 0.05). Inverse associations were identified between RBC membrane monounsaturated fatty acids (MUFAs) (β = −0.88,p< 0.01), dietary polyunsaturated fatty acids (PUFAs) (β = −0.21,p< 0.05) and CRP, and the Australian Eating Survey Modified Mediterranean Diet (AES-MED) score and IL-6 (β = −0.21,p< 0.05). In summary, using both objective and subjective measures of fat intake and diet quality, our study has confirmed a positive association between saturated fat and inflammation, while inverse associations were observed between MUFAs, PUFAs, the Mediterranean diet, and inflammation. Our results provide further evidence that manipulating diet quality, in particular fatty acid intake, may be useful for reducing chronic systemic inflammation.